Hepatitis C virus (HCV) is diffused worldwide, and it is responsible for potentially severe chronic liver disease and primary liver cancer. Chronic infection remains for life if not spontaneously eliminated and viral persistence profoundly impairs the efficiency of host’s immunity. Attempts have been made to develop an effective vaccine, but efficacy trials have met with failure. The availability of highly efficacious direct acting antivirals (DAA) has shed hopes for progressive elimination of chronic HCV infection; however, this approach requires a global monumental effort. Moreover, DAA treatment does not completely restore the normal immunologic homeostasis. Here we discuss the main immunological features of immune responses to HCV and the epigenetic scars that chronic viral persistence leaves behind.

Background: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. Aims: This narrative review analyzes the literature about: a) the duration of natural immunity; b) cellular immunity; c) cross-reactivity; d) the duration of post-vaccination immune protection; e) the probability of reinfection and its clinical manifestations in the recovered patients; f) comparisons between vaccinated and unvaccinated in the possible reinfections; g) the role of hybrid immunity; h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; i) comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. Material and Methods: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. Results: nearly 900 studies were collected and 238 pertinent articles were included. It was highlighted that the vast majority of individuals after COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. Conclusions: this narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: a) measure the durability of immunity over time; b) evaluate both the impacts of Omicron-5 on vaccinated and healed subjects and of hybrid immunity.

Optimal detection strategies for effective convalescent immunity after SARS-CoV-2 infection and vaccination remain unclear. The objective of this study was to characterize convalescent immunity targeting the SARS-CoV-2 spike protein using a multiparametric approach. At the beginning of the pandemic, we recruited 30 COVID-19 unvaccinated convalescent donors and 7 unexposed asymptomatic controls. Peripheral blood mononuclear cells (PBMCs) were obtained from leukapheresis cones. The humoral immune response was assessed by measuring serum anti-SARS-CoV-2 spike S1 subunit IgG semiquantitative ELISA and T cell immunity against S1 and S2 subunits were studied by IFN-γ Enzyme-Linked Immune absorbent Spot (ELISpot), flow cytometric (FC) activation-induced marker (AIM) assays and the assessment of cytotoxic CD8+ T-cell function (in the subset of HLA-A2 positive patients). No single immunoassay was sufficient in identifying anti-spike convalescent immunity among all patients. There was no consistent correlation between adaptive humoral and cellular anti-spike responses. Our data indicate that the magnitude of anti-spike convalescent humoral and cellular immunity is highly heterogeneous and highlights the need for using multiple assays to comprehensively measure SARS-CoV-2 convalescent immunity. These observations might have implications for COVID-19 surveillance, and optimal vaccination strategies for emerging variants. Further studies are needed to determine the optimal assessment of adaptive humoral and cellular immunity following SARS-CoV-2 infection, especially in the context of emerging variants and unclear vaccination schedules.

Innate immune pathways play a crucial role in the development of atherosclerosis, from sensing initial danger signals to the long-term reprogramming of immune cells. Despite the success of lipid-lowering therapy, anti-hypertensive medications, and other measures in reducing complications associated with atherosclerosis, cardiovascular disease (CVD) remains the leading cause of death worldwide. Consequently, there is an urgent need to devise innovative preventive and therapeutic strategies to alleviate the global burden of CVD. Extensive experimental research and epidemiological studies have demonstrated the dominant role of innate immune mechanisms in the progression of atherosclerosis. Recently, landmark trials including CANTOS, COLCOT, and LoDoCo2 have provided solid evidence, demonstrating that targeting innate immune pathways can effectively reduce the risk of CVD. These groundbreaking trials mark a significant paradigm shift in the field and open new avenues for atheroprotective treatments. It is therefore crucial to comprehend the intricate interplay between innate immune pathways and atherosclerosis for the development of targeted therapeutic interventions. Additionally, unraveling the mechanisms underlying the long-term reprogramming may offer novel strategies to reverse the pro-inflammatory phenotype of immune cells and restore immune homeostasis in atherosclerosis. In this Review, we present an overview of the innate immune pathways implicated in atherosclerosis, with a specific focus on the signaling pathways driving chronic inflammation in atherosclerosis and the long-term reprogramming of immune cells within the atherosclerotic plaque. Elucidating the molecular mechanisms governing these processes presents exciting opportunities for the development of a new class of immunotherapeutic approaches aimed at reducing inflammation and promoting plaque stability. By addressing these aspects, we can potentially revolutionize the management of atherosclerosis and its associated cardiovascular complications.

The OPV is the vaccine of choice in polio eradication, especially in developing countries, as it has eliminated the wild poliovirus type 2. However, the immunity induced by IPV is better than that induced by the OPV. The present study compared the mucosal and humoral response to poliovirus vaccines administered to previously OPV-immunized children to assess the immunity gap in children at-risk of high poliovirus transmission. This was a community-based three-arm cluster randomized controlled trial conducted from June 2013 to May 2014 in healthy children under five years of age living in three high-risk districts of Pakistan, i.e., Karachi, Kashmore, and Bajaur. 387 clusters were randomized (131 to arm A, 127 to arm B, and 129 to arm C); however, 360 remained in the trial until the end (116 in arm A, 122 in arm B, and 122 in arm C). These clusters were randomly allocated using a computer algorithm to receive routine polio program (bOPV) activities (control, arm A), additional interventions with community mobilization and provision of short-term preventive maternal and child health services and routine immunization, including bOPV via health camps, (arm B), or all interventions of arm B with an additional provision of IPV (arm C ~ bOPV and IPV). Blood and stool samples were collected from a sub-sample to estimate humoral and intestinal immunity. Study findings showed that the serum titers were highest in Group C (IPV+OPV) at the baseline for P1, where its increase over time was also more prominent. Titers for P2 and P3 were statistically significantly higher amongst those who had received a routine OPV dose versus those who had not; this was true for all study groups and visits. In populations with high Oral Polio Vaccine (OPV) failure rates, administering an Inactivated Polio Vaccine (IPV) booster after a minimum of two OPV doses may effectively bridge immunity gaps. The IPV alone offers limited benefits to humoral immunity and doesn't provide intestinal immunity to prevent the infection and propagation of live poliovirus among unexposed populations.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.

Recently, two pig-to-human kidney transplants and a pig-to-human heart transplant were completed. The kidney trials involved a patient who was deceased and a patient who was brain dead. They seemed to indicate that pig kidneys can be at least somewhat functional in humans. However, patients still have to be under severe immunosuppression - and the first patient to receive a porcine heart passed away after two months. It is difficult to know exactly which proteins we need to overexpress or underexpress/knockout in a porcine organ to negate the human recipient’s immunological response to it. And testing different porcine organ genetic modifications in baboons can cost around $500,000 per transplant. But there might be a way to decrease immunogenicity where we don’t have to worry so much about modifying the animal’s organs genetically. First, however, we would have to prevent complement factor-mediated lysis of the porcine vascular endothelial cells, which we have made much progress on with triple knockout animals. Then, we could modify the porcine organ so that the cells of said organ secrete a small molecule or peptide that acts as a chemorepellent for the host immune cells. The host immune cells can be modified via bone marrow transplant or vector delivery to express the chemorepulsion receptor.

Most studies on vaccines of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on antibody, but cellular immunities are also critical. We aimed to evaluate the immune reactions of hemodialysis (HD) patients after the administration of the booster dose from the perspective of both humoral and cellular immunities. Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (control group) receiving three doses of BNT162b2 vaccine were measured for anti-SARS-CoV-2 immunoglobulin (IgG) and T-SPOTⓇ.COVID test (T-SPOT) before, 3 weeks, and 3 months after the booster dose. The HD group had significantly higher SARS-CoV-2 IgG levels 3 weeks and 3 months after the booster dose than the control group, although both groups had no difference in SARS-CoV-2 IgG levels before the booster dose. Moreover, the HD group had significantly higher T-SPOT levels before and 3 weeks after the booster dose than the control group, but the difference was not significantly different 3 months after the booster dose. Furthermore, the incidence rates of local and systemic adverse reactions were significantly higher in the HD group than in the control group. HD patients obtained higher SARS-CoV-2 IgG levels and SARS-COV-2-specific T-cell responses after the booster dose than control.

We analyze the Covid-19 mortality scenario in India and compare it with those in other large-population regions such as Asia-excluding-China, Africa, European Union, South America, and USA. We compare existing fatality data and offer an interpretation for low fatality based on immunity due to endemic malaria and TB. We identify the hot climate in the past summer as a possible cause for low death count in southern-hemisphere countries without endemic malaria and TB. We also make India-specific observations for easing the lockdown and estimations for the time required to attain herd immunity. Whatever optimism we present should be viewed as a guarded optimism. There should not be room for complacency.

The main problem in creating anti-coronavirus vaccines that target mainly proteins of the outer membrane of the virus remains the rapid variability of the RNA genome of the pathogen that encodes these proteins. In addition, the introduction of technologies that can provide affordable and fast production of flexible vaccine formulas that easily adapt to the emergence of new subtypes of SARS-CoV-2 is required. Universal oligonucleotide vaccine can take into account the dynamics of rapid changes in the virus genome, as well as be synthesized on automatic DNA synthesizers in large quantities in a short time. In this brief report, the effectiveness of four phosphorothioate constructs of the La-S-so type oligonucleotide vaccine will be evaluated for the first time on transgenic mice [B6.Cg-Tg (K18-ACE2)2]. In our primary trials, the oligonucleotide vaccine increased the survival rate of animals infected with SARS-CoV-2 and also reduced the destructive effects of the virus on the lung tissue of mice. The obtained results show the perspective of the development of vaccine constructs of the La-S-so type for the prevention of coronavirus infections, including those caused by SARS-СoV-2.

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as “Whether there are differences based on gender in risk and severity of infection or mortality rate?” and “What are the biological explanation and mechanisms underlying these differences?” Emerging evidence has proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. From an immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.

The human body tries to tolerate the pigment-producing cells through several mechanisms including; central deletion of melanocyte-specific T cells or peripheral induction of inhibition or anergy of the released cytotoxic T cells. The melanocytes also try to hide their antigenic components from the immune system. The breakdown of these mechanisms leads to the induction of the adaptive immunity and the production of unopposed melanocyte-specific cytotoxic T cells, destroying the melanocytes, leading to the development of depigmentation. Vitiligo will develop whenever tolerance-jeopardizing factors outnumber or over-weigh the tolerance-inducing factors.

Mycobacterium tuberculosis complex causes tuberculosis (TB), a disease that causes pulmonary inflammation but can also affect other tissues. Despite macrophages having a defined role in TB immunopathogenesis, other innate immune cells, such as neutrophils, are involved in this process. These cells have high phagocytic ability and a microbial-killing machine comprised of enzymes, antimicrobial peptides, and reactive oxygen species. In the last two decades, a new neutrophil immune response, the neutrophil extracellular traps (NETs), has been intensely researched. NETs comprise DNA associated with histones, enzymes, and antimicrobial peptides. These structures are related to antimicrobial immune response and some immuno-pathogenesis mechanisms. This mini review highlights the role of NETs in tuberculosis and how they can be helpful as a diagnostic tool and/or therapeutic target.

Shrimps are under the influence of several environmental factors such as fluctuation of physical and chemical parameters of the water affected by variations in rainfall, temperature, salinity, and pH. These factors have also been identified as risk factors for shrimp disease outbreaks. Despite the high levels of production, shrimp producers suffered significant economic losses in years, mainly due to the presence of diseases that now plague the industry. In particular, viral diseases have had and will continue to have profound impact on industry growth. In response to stress such environmental or pathophysiological, cells are able to up regulating selectively the expression of a protein group known as Heat Shock Proteins (HSPs). In a recent search at the literature we observed a close relation between HSP70 with apoptotic proteins and others stress proteins such HSP60 and HSP90. Moreover, the response of shrimp to viral stress was examined, some of which are correlated to the reactions of HSP70. Thus, the aim of this review is to describe the current knowledge on the status of stress responses in shrimps, particularly HSP70 responses, triggered by viruses.

We have proposed a model considering two equally sized population (group A and group B) with low and high levels of disease tolerance. We have argued that in the more tolerant group (group B) the progression of the disease with respect to time will be slow with lower number of infections at any given time. We attribute this effect to the innate immunity which advantageously, can also be one of the major contributing factors for flattening the curve. We have compared the growth of Covid-19 disease in various countries to understand this effect.

Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodeling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease via the double methylation of the 5' end of eukaryotic DNA or RNA-based viral genomes, the 7-MeGpppA2’-O-Me cap, and its double methylation capping process is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16) and by N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered that polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), and consequently, detection of Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs) alike. NSP1 also silences important interferon-encoding genes (INGs) and interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Another important viral NSP is NSP14, as it plays two functional roles that are independent of each other; to produce new viral genetic material for the purpose of maintaining the validity of the viral genome as well, and not just transfer a methyl group to the 5’ end of the viral genome. Other viral NSPs share a role with NSP1, 10, 14 and 16 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases.

This study compared the relative effect of two trace mineral supplementation strategies recom-mended in France for newborn beef calves. 600 calves were supplemented with 20 mg oral sele-nium (OTM group) at birth (D0) or by injection (ITM group) of a multi-mineral solution (60 mg of Zn, 10 mg of Mn, 15 mg of Cu, 5 mg of Se) on D0, D30 and D60. Mortality and the incidence rate of diseases, including diarrhea, omphalitis, pneumonia, as well as medicinal treatments, were recorded from D0 to D210. The incidence rate of omphalitis was significantly lower in the ITM group than in the OTM group (respectively 11% vs. 17%, P = 0.036). The cumulative inci-dence rate of all health troubles was lower in the ITM group than in the OTM group (P=0.007). Except for pneumonia, incidence of diarrhea (24% vs. 22%), use of oral (7% vs. 6%) or IV rehydra-tion therapy (4% vs. 2%) or use of antibiotics (43.3% vs. 38.0%) and mortality (3% vs 2%) were numerically higher in OTM group than in ITM group (n.s.). In this study, ITM supplementation is as efficient as oral supplementation regarding calves' health status. It reduces the risk of ompha-litis at the calf level effectively.

Neurodevelopmental disorders are characterised by an amalgam of genetic and epigenetic faults implicating neuronal protein-related loss-of-function and gain-of-function respectively, hence their inclusion into the category of complex diseases. Neurodevelopmental disorders are regarded as autism spectrum disorder due to this reason; that the risk factors and phenotype constitute a spectrum of faults and protein overactivity. One example of an epigenetic factor leading to the onset of neurodevelopmental delays constitutes a set of immune response-based dysregulations, as well as the excessive growth of the adaptive immune memory of the foetus or the baby following significant infectious disease during pregnancy, as well as in babies aged 0-2, given the existence of profound links between developmental immunity and developmental neurology. Given that genetic information very likely represents a form of energy, the intake of excessive pathogen-related information may transiently overload the adaptive immune memory similarly to the manner functional pathogens do whilst inducing significant illness, and if events as such occur during important stages of neuro-immunological development, then there could often be irreversible effects upon the rate of development in neurological networks that normally have a major importance in the modulation of the related cognitive and behavioural phenotype. The full extent of evidence may only be obtained via a thorough study of the applications of physical laws into biology and medicine, given the foundational role of the physical matter in the development and maintenance of life. A common misconception is that neurodevelopmental delays are characterised solely by an accumulation of protein loss-of-function incidences in the central nervous system area, rather than a disruption of neuronal region developmental rates. For example, an overexpression of neuronal proteins related to cognition factors that is accompanied by an underexpression of proteins related to social behaviour is phenotypically manifested in people with sharper rational thinking and poorer communication skills, with an impact on the abilities of decision-making as well, and this tends to be regarded as a classical example of the clinical manifestation of neurodevelopmental delays. More severe forms of autism spectrum disorder tend to implicate a more generalistic impact upon the developmental rates of key human behaviours, including those related with the development and maintenance of social and intimate relationships. Likewise, more severe implications upon regular developmental rates tend to bring a major impact upon the healthy function of related functions. As a result, lower functioning forms of neurodevelopmental delays bring fresh concerns with regards to a possible uncanny increase of incidences of deviated sexuality during years of adulthood, and in the worst cases, such deviations may lead to the planning and development of criminal activity, particularly in individuals who are or become prone to breaking the moral code that established the civilised society. What holds the concerns valid is the exponential increase in the number of lower functioning autism cases throughout the world and the major signs that such an increase will continue with a full force. One major solution to this potential future problem would be a much higher investment into awareness of the exact genetic and environmental factors that directly or indirectly result in the onset of lower-functioning autism and of the current research efforts to develop the matching support for people found in situations as such. The most important aim of future research with regards to such a scenario would be a separation of disease and disability with choices made to step into more severe forms of disease and into areas that are outside of the established moral circle.

Coronaviruses are highly transmissible and pathogenic viruses for humans and animals. The vast quantity of information collected about SARS-CoV-2 during the pandemic helped to unveil details on the mechanisms behind the infection, which are still largely elusive. Recent research demonstrated that different class I/II human leukocyte antigen (HLA) alleles might define an individual susceptibility to SARS-CoV-2 spreading, contributing to the differences in the distribution of the infection through different populations; additional studies suggested that the homolog of the HLA in cats, the Feline Leukocyte Antigen (FLA), plays a pivotal role in the transmission of viruses. With these premises, this study aimed to exploit a bioinformatic approach for the prediction of the transmissibility potential of two distinct Feline Coronaviruses (FCoVs) in domestic cats (Feline enteric Coronavirus, FeCV and Feline Infectious Peritonitis Virus, FIPV) using SARS-CoV-2 as the reference model. We performed an epitope mapping of nonapeptides deriving from SARS-CoV-2, FeCV and FIPV glycoproteins and predicted their affinities for different alleles included in the three main loci in class I FLAs (E, H and K). The predicted complexes with the most promising affinities were then subjected to molecular docking and molecular dynamics simulations to provide insights into the stability and binding energies in the cleft. Results showed the FLA proteins encoded by alleles in FLA-I H (H*00501 and H*00401) and E (E*01001 and E*07001) loci are largely responsive to several epitopes deriving from replicase and spike proteins of the analyzed coronaviruses. The analysis of the most affine epitope sequences resulting from the prediction can stimulate the development of anti-FCoV immunomodulatory strategies based on peptide drugs.

Background Despite the high vaccination coverage rate, in-hospital transmission of measles continues to occur in South Korea. We present a measles outbreak in which two healthcare workers (HCWs) with presumptive evidence of measles immunity were infected by a patient with typical measles at a single hospital in South Korea. This facilitated the evaluation of measles seroprevalence in all HCWs. Methods In 2018, suspected patients and contacts exposed during a measles outbreak were investigated based on their medical histories and vaccination status. Cases were confirmed by the detection of measles-specific immunoglobulin M or RNA. After the measles outbreak, all HCWs underwent measles IgG testing for point-prevalence surveillance. In addition, we have routinely performed measles IgG tests on new HCWs since 2019. The measles vaccine was administered to HCWs who tested negative or equivocally negative for IgG antibodies. Results An index patient who returned from China with fever and rash was diagnosed with measles at a hospital in Korea. Two additional HCWs were revealed as measles cases: one was vaccinated with the 2-dose measles–mumps–rubella (MMR) vaccine, and the other, who was born in 1967, was presumed to have immunity from natural infection in South Korea. All three patients harbored the same D8 genotype. No additional measles cases were identified among the 964 contacts of secondary patients. After the measles outbreak, 2,310 HCWs underwent measles IgG tests. The average age at the time of the test was 32.6 years, and 74.3% were female. The overall seropositivity of measles was 88.9% (95% confidence interval, 87.5 –90.1). Although the birth cohorts between 1985 and 1994 were presumed to have received the measles-rubella (MR) catch-up vaccination in 2001, 175 (89.3%) HCWs were born after 1985 among the 195 seronegative cases. Conclusion Despite high population immunity, imported measles transmission occurred among HCWs, with presumed immunity. This report underscores the importance of understanding the prevalence of measles susceptibility among newly employed HCWs. This is important for policymaking regarding hospital-wide vaccinations to prevent vaccine-preventable diseases.

We investigate a new fundamental property of infectious diseases with natural adaptive immunity that weakens over time. Numerical experiments with a model of the Covid-19 epidemic in Moscow have demonstrated that when the reproduction number R0 is about 4, a qualitative change (bifurcation) occurs in the behavior of the virus-human system. Below this value, the long-term forecast tends to undamped oscillations; above it, the forecast shows damped oscillations: the amplitudes of epidemic waves decrease gradually, with a constant, very high background level of morbidity that keeps the natural immunity near 100%. To confirm this result analytically, we use an original modification of the Euler-Lotka renewal equation, which describes the dynamics of infected patients distributed by disease duration (time since infection) and accounts for immunity. To construct a bifurcation diagram, which illustrates the dependence of the equilibrium stability on the parameter R0, we linearize the equation in the vicinity of the equilibrium point and examine its numerical approximation (discrete form). This approximation can be interpreted as a Leslie model, with the matrix elements dependent on the parameter R0. By examining the roots of the corresponding Lotka polynomial, we can assess the stability of the equilibrium point. For the bifurcation diagram, we use the functions obtained from the simulation of the Covid-19 epidemic in Moscow. However, observations of the epidemic in other cities and countries support the primary finding of our study regarding the attenuation of epidemic waves.

Compartmental models that dynamically divide the host population in categories such as susceptible, infected and immune constitute the mainstream of epidemiological modelling. Effectively such models treat infection and immunity as binary variables. We constructed an individual based stochastic model that considers immunity as a continuous variable and incorporates factors that bring about small changes in immunity. The small immunity effects (SIE) comprise cross immunity by other infections, small increments in immunity by sub clinical exposures and slow decay in the absence of repeated exposure. The model makes qualitatively different epidemiological predictions including repeated waves without the need for new variants, dwarf peaks (peak and decline of a wave much before reaching herd immunity threshold), symmetry in the upward and downward slopes of a wave, endemic state, new surges after variable and unpredictable gaps, new surge after vaccinating majority of population. In effect the SIE model raises alternative possible causes of the universally observed dwarf and symmetric peaks and repeated surges, observed particularly well during the Covid-19 pandemic. We also suggest testable predictions to differentiate between the alternative causes for repeated waves. The model further shows complex interactions of different interventions that can be synergistic as well as antagonistic. The model suggests that interventions that are beneficial in the short run can also be hazardous in the long run.

Staphylococci sp. have become the primary pathogens implicated in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations and the protracted course the infections may take, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. 35 studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. Ameliorating these molecular pathways may serve as a therapeutic avenue for the prevention and treatment of these infections in near future.

The interaction of the nervous, immune, and endocrine systems is crucial in the maintenance of homeostasis in vertebrates, and vital in mammals. The spleen is a key organ that regulates the neuroimmunoendocrine system. The Taenia crassiceps mouse system is an excellent experimental model to study the complex host-parasite relationship, particularly sex-associated susceptibility to infection. The aim of the present study was to determine the changes in neurotransmitters, cytokines, sex steroids, and sex-steroid receptors in the spleen of cysticercus-infected male and female mice, and the association of these different components with whole parasite counts. We found that parasite load was higher in female in comparison to male mice. The levels of the neurotransmitter epinephrine were significantly decreased in infected male animals. The expression of IL-2 and IL-4 in the spleen was markedly increased in infected mice; however, the expression of Interleukin (IL)-10 and Interferon (IFN)-γ decreased. We also observed sex-associated differences between non-infected and infected mice. Interestingly, the data show that estradiol levels increased in infected males but decreased in females. Our studies provide evidence that infection leads to changes on neuroimmunoendocrine molecules in the spleen during infection. These changes are dimorphic and impact the establishment, growth, and reproduction of T. crassiceps. Our findings support the key role of the neuroimmune network in determining sex-associated susceptibility to the helminth parasite.

We have analysed the death and recovery rate of Covid-19 disease progression. From the analysis, we have argued that the pandemic is over in certain countries (labelled as group-A) and for other countries (labelled as group-B) the disease appears to remain as endemic. Taking into account the serological survey (sero-survey) test results obtained by certain groups and comparing it with herd immunity threshold value one can infer that the low number of infection for group-B is either due to acquired immunity by some previous infection by other coronavirus or due to innate immunity towards this infection. This effect is stronger for group-B to slow the progress of the disease to such an extent resulting in flattening of the disease progression curve compared to group-A.

Mammalian species possess sophisticated innate immune mechanisms that collectively combat a wide array of viral pathogens. Among these, the well-characterized interferon (IFN) response has been extensively researched; however, the role of antiviral RNA interference (RNAi) in mammals is emerging as an area of significant interest. Previous research has noted that Dicer, an enzyme crucial for processing double-stranded RNA (dsRNA), exhibits reduced activity in vitro, and that the IFN response may overshadow or inhibit the antiviral functions of RNAi in mammalian cells. Consequently, the functional relevance of RNAi in antiviral defense within mammalian somatic cells remains an open question. The evolution of antiviral systems in human populations reflects their substantial advantages, paralleling the evolutionary pressure on genomes encoding such defense mechanisms. While the well-studied protein-guided immune responses in mammals are essential for survival in viral environments, small RNA-mediated antiviral systems, which utilize complementary base pairing to silence non self-genetic material, also play a crucial role. In mammals, evidence suggests that microRNAs (miRNAs) regulate genes integral to antiviral responses, and emerging data indicate that small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNAs (tRNAs) can directly target virus-derived nucleic acids. This review aims to highlight some of the recent progress in understanding mammalian antiviral RNAi mechanisms.

Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.

Viral infection activates the transcription factors IRF3 and NF-κB, which synergistically induce type I interferons (IFNs). Here, we identify the E3 ubiquitin ligase RNF138 as an important negative regulator of virus-triggered IRF3 activation and IFN-β induction. Overexpression of RNF138 inhibited virus-induced activation of IRF3 and transcription of the IFNB1 gene, whereas knockout of RNF138 promoted virus-induced activation of IRF3, and transcription of the IFNB1 gene. We further found that RNF138 promotes ubiquitination of PTEN and subsequently inhibits PTEN interactions with IRF3, which is essential for PTEN-mediated nuclear translocation of IRF3, thereby inhibiting IRF3 import into the nucleus. Our findings suggest that RNF138 negatively regulates virus-triggered signaling by inhibiting the interaction of PTEN with IRF3, and these data provide new insights into the molecular mechanisms of cellular antiviral responses.

During last decades, production and consumption of small ruminant milk has been increased. As a result of it, sheep and goat farming has been developing and scientists are focused on these animal researches both clinical and feeding strategies. By the evolutionary challenges and adaptations, colostrum has a crucial role of immune complementation for litter. As a result of these challenges and adaptations neonatal life is especially more important in ruminants because of it affects their whole life and future of livestock. Passive immune transfer is the main mechanism that explained by biological evolution between dam and lamb and also it is effected by factors up to dam and up to the litter. Today importance of passive immune transfer is well known for the future of livestock economy and animal welfare. In the literature, researchers are focused on correlation between colostrum quality (especially immunoglobulin amounts) and blood serum levels of newborns. Aims of present review are to discuss datas of recent studies, point out different effecting factors in colostrum quality and passive immune transfer, enlighten and give new ideas to researchers.

Epithelial ovarian cancer is an aggressive disease of the female reproductive system and a leading cause of cancer death in women. Standard of care includes surgery and platinum-based chemotherapy yet patients continue to experience a high rate of recurrence and metastasis. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment in highly selective patients extends overall survival by nearly 12 months. The clinical studies are highly supportive of the use of HIPEC in the treatment of ovarian cancer though the therapeutic approach is limited to academic medical centers. The mechanism underlying HIPEC benefit remains unknown. The efficacy of HIPEC therapy is impacted by several procedural and patient/tumor factors including the timing of surgery, platinum sensitivity, and molecular profiling such as homologous recombination deficiency. The present review aims to provide insight into the mechanistic benefit of HIPEC treatment with a focus on how hyperthermia activates the immune response, induces DNA damage and impairs DNA damage repair pathways, and has a synergistic effect with chemotherapy, with the ultimate outcome of increasing chemosensitivity. Identifying the points of fragility unmasked by HIPEC may provide the key pathways that could be the basis of new therapeutic strategies for ovarian cancer patients.

The effects of ELICE16INDURES, a well-known plant conditioner developed by the Research Institute for Medicinal Plants and Herbs Ltd. Budakalasz, Hungary, were studied in a soybean population. The active ingredients of the compound have been selected to help elicit general immunity in plants without pathogenic damage, thereby roborizing the healthy plant population and preparing it for possible future biotic stressors. Here we have analyzed changes in the expression levels of genes encoding enzymes involved in the catalysis of metabolic pathways that induce and regulate PAMP-triggered immunity (PTI) at two different time points and treatments. Twenty-three different enzymes were analyzed that catalyze different metabolic pathways, such as the biosyntheses of jasmonic acid, salicylic acid, ethylene, phenylpropanoid, flavonoid, and phytoalexin biosynthesis and cellular detoxification processes. Bioinformatical softwares werw used to analyze the results. It has been found that some of the primary defense mechanisms (e.g., Mitogen-Activated-Protein Kinase (MAPK) cascade, jasmonic acid biosynthesis, flavonoid and phytoalexin biosynthesis, etc.) that intensify following the attack of pathogens can be activated without the intrusion of the actual pathogen by an immunochemical. Thus, we proved that plant resistance can be artificially conditioned.

Neutrophils as innate immune cells primarily act as first responders in acute infection and directly maintain inflammatory responses. However, a growing body of evidence suggests that neutrophils also bear the potential to mediate chronic inflammation by exhibiting memory-like features. We recently showed that priming by serial doses of lipopolysaccharide (LPS) from gram-negative bacteria can trigger opposing memory-like responses (exaggerated inflammation, i.e. trained sensitivity or suppression of inflammation, i.e. tolerance) depending on the LPS-dose. We now asked whether this observation could also hold true for lipoteichoic acid (LTA) from gram-positive S. aureus. We found comparable effects of LTA on neutrophil priming as seen for LPS. Low-dose (1 ng/mL) LTA-priming promoted increased production of pro-inflammatory mediators (i.e., TNF-α, IL-6, ROS), whereas high-dose (10 µg/mL) results in contrary reactions supporting anti-inflammatory responses by increased IL-10 and declined pro-inflammatory capacity. In vitro neutrophil recruitment was similarly regulated by LTA -priming. Investigation of signalling patterns revealed TLR2/MyD88-mediated regulation of NFκB-p65 through intermediate PI3Ks/MAPK. Collectively, our data suggest a previously unknown capacity of neutrophils to be differentially primed by varying doses of LTA, endorsing memory-like features in neutrophils.

Infection by human immunodeficiency virus type I (HIV-1) requires virus particle binding to host cell-surface receptor CD4 via the viral envelope glycoprotein gp120. HIV-1 therapy and prevention efforts involve development of mimetic or recombinant gp120 vaccines or deployment of antiviral agents that target specific epitopes of gp120. The unliganded conformational state of gp120 is closed, whereas the CD4-bound state is open. However, in between, there exist dynamic conformational states, indicating intrinsically flexible region(s) of structural dynamics, imposing a structural challenge for developing drug or antibody targets. Known conformational states of gp120 were determined by X-ray crystallographic and cryo-electron microscopy, and neither method captures the population of gp120 species arising from conformational plasticity, motions, and transitions. gp120 plasticity brings up several important questions. How will differences in conformation affect receptor binding, antibody recognition, and neutralization? Which regions are crucial for gp120 structural plasticity? How could structural dynamics influence HIV-1 evasiveness against host immunity and drugs or vaccines, and facilitate the viral entry into its host? This review explores the structural constraints presented by conformational states of the glycoprotein to antibodies or drugs and how these conformational states provide structural avenues for the virus to escape neutralizing agents and evade host immunity.

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system–related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate antiviral effect for the exosomes of teleost fish. Exosomes were isolated from mandarin fish serum by ultracentrifugation could internalize into Mandarin fish fry (MFF-1) cells and inhibited Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigated the underlying mechanisms of exosomes in inhibiting ISKNV infection. The protein composition of serum-derived exosomes was by analysis mass spectrometry and found that myxovirus resistance 1 (Mx1) was incorporated in the exosomes. Furthermore, the scMx1 protein was proved transferred to the recipient cells though the exosomes. Our results found that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication and suggested an underlying mechanism of the serum-derived exosomes antivirus is that serum-derived exosomes incorporation of the Mx1 protein into exosomes and delivery into recipient cells. This study provided an evidence for the important antiviral role of exosomes in the immune system of teleost fish.

Salivarian trypanosomes are extracellular parasites affecting humans, livestock and game animals. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense are human infective sub-species of T. brucei causing Human African Trypanosomosis (HAT - sleeping sickness). The related T. b. brucei parasite lacks the resistance to survive in human serum, and only inflicts animal infections. Animal Trypanosomosis (AT) is not restricted to Africa, but is present on all continents. T. congolense and T. vivax are the most widespread pathogenic trypanosomes in sub-Sahara Africa. Trough mechanical transmission, T. vivax has however been introduced into South America. T. evansi is a unique animal trypanosome that is found in vast territories around the world and can cause atypical Human Trypanosomosis (aHT). All salivarian trypanosomes are well adapted to survival inside the host’s immune system. This is not a hostile environment for these parasite, but this is the place where they thrive. Here we provide an overview of the latest insights into the host-parasite interaction and the unique survival strategies allowing trypanosomes to outsmart the immune system. In addition, we review new developments in treatment and diagnosis as well the issues that have hampered the development of field-applicable anti-trypanosome vaccines for the implementation of sustainable disease control.

After the influenza H1N1 pandemic of 2009, the seasonal A/Brisbane/59/2007 strain was replaced by the A/California/07/2009 strain for the influenza virus vaccine composition. After several seasons with no indications on the occurrence of antigenic drift, A/Michigan/45/2015 was chosen as the H1N1 vaccine strain for season 2017/2018. Since the immune response to influenza is shaped by the history of exposure to antigenically similar strains, the potential cross-protection between seasonal human influenza vaccine strains and the emerging pandemic strains was investigated. Human serum samples were tested by haemagglutination inhibition and single radial haemolysis assays against A/Brisbane/59/2007, A/California/07/2009, and A/Michigan/45/2015 strains. Strong cross-reactions between A/California/07/2009 and A/Michigan/45/2015 strains were observed in 2009/2010, most likely induced by the start of the 2009 pandemic, and the subsequent post-pandemic seasons from 2010/2011 onwards when A/California/07/2009 becomes the predominant strain. In 2014/2015 season, population immunity against A/California/07/2009 and A/Michigan/45/2015 strains increased again, associated with strong cross-reactions. While haemagglutination inhibition assay has a higher sensitivity for detection of new seasonal drift, the single radial haemolysis assay is an excellent tool to determine the presence of pre-existing immunity, allowing a potential prediction on the booster potential of influenza vaccines against newly emerging drifted strains.

There is a global rise in the emergence of infectious diseases and the enigmatic coronavirus disease 2019 (COVID-19) being the most recent one. It is ravaging the world with little understanding of its etiology and factors affecting its transmission dynamics. Meanwhile, seasonal variations in weather are major factors impacting infectious disease transmission patterns. Developing countries are likely to be most affected by weather changes, largely because of challenges such as inadequate drainage and sewage management systems, healthcare facilities, education, and funding to efficiently mitigate infectious diseases. In Nigeria, weather conditions alternate between rainy and dry seasons. Conditions such as rainfall, flood, and humidity have been reported to influence infectious disease transmission. Thus, understanding the impact of weather changes in transmission dynamics and immune response to COVID 19 will help in preventive measures and policy making to curtail its spread most especially in Nigeria as the rainy season fully sets in.

The tissue micro environment or milieu consists of a highly dynamic population of cellular and non-cellular components which constitute a complex regulatory network aimed at maintaining the organ homeostasis. In the modern medicine the discovery of miRNAs is undoubtedly a promising field of research and they are essential in orchestrating immune system logic and their release in the gut micro milieu can directly affect bacterial gene expression. Here, we briefly review the role of microRNAs, focuses on their role on immune system components in physiological and pathophysiological gut micro milieu.

Background. Waning of neutralizing and cell-mediated immune response after the primary vac-cine cycle (PVC) and the first booster dose (BD) is of concern, especially for PLWH with a CD4 count ≤200 cells/ mm3.Methods.Neutralizing antibodies (nAbs) titers by microneutralization assay against WD614G /Omicron BA.1 and IFNγ production by ELISA assay were measured in samples of PLWH at 4 time points [2 and 4 months post-PVC (T1 and T2), 2 weeks and 5 months after the BD (T3 and T4)]. Participants were stratified by CD4 count after PVC (LCD4, <200/mm3; ICD4, 201-500/mm3 and HCD4, >500/mm3). Mixed models were used to compare mean responses over T1-T4 across CD4 groups. Results. 314 PLWH on ART (LCD4=56; ICD4=120; HCD4=138) were enrolled. At T2, levels of nAbs were significantly lower in LCD4 vs ICD4/HCD4 (p=0.04). BD was crucial for increasing nAbs titres above 1:40 at T3 and up to T4 for WD614G. A positive T cell response after PVC was observed in all groups, regardless of CD4 (p=0.31). Conclusions. Waning of nAbs after PVC was more important in LCD4 group. BD managed to re-establish higher levels of nAbs against WD614G which were retained for 5 months. The level of T-cellular response was significantly higher in HCD4 and ICD4 compared to the LCD4 group although it remained above detectable levels over the entire study period regardless of CD4 count. Keywords: HIV-1 infection; SARS-CoV-2 infection;

As an extraordinarily diverse group of bacteria, lactobacilli are now placed in several genera which names still contain “lactobacillus” in their core. Despite the names, this group of the lactic acid bacteria comprises microorganisms which are very important for our life especially in early development of the human microbiota and immune system. The interactions of the lactobacilli with elements of the mucosal immunity leads to its shaping and development, which is recognized as a potential driving force in the evolution of the human immune system. Although most of the evidence supporting the idea of the leading role of lactobacilli in housekeeping of the human health derives from articles on probiotics aiming to elucidate mechanisms of their functional activities and studies on mucosal immunity on germ-free mice, it is justifiable to extend observations on properties of the individual probiotic Lactobacillus related to health benefits onto other strains sharing common characteristic of the species. In this review, we will discuss acquisition, presence and functions of lactobacilli in different human microbiota throughout the whole life including those arising in amnion and their interactions with mucosal and immune cells. Examples of immune system modulation by probiotic lactobacilli due to competition for available nutrients in the colon, colonization site interference, and competition for binding sites on gut epithelial cells, production of bacteriocin, lowering of colonic pH, and nonspecific stimulation of the immune system will be shown.

Background: Understanding factors associated with protective immunity against emerging viral infections is crucial for global health. Pakistan reported its first COVID-19 case on February 26, 2020, but compared to other countries, it experienced relatively low COVID-19-related morbidity and mortality between 2020 and 2022. The underlying reasons remain unclear. Our research aims to shed light on this crucial issue. Methods: We conducted serial household surveys over 16 months (Rounds 1-4, July 2020 - November 2021) in urban (Karachi) and rural (Matiari) Sindh, sampling 1100 households and 3900 individuals. Our comprehensive approach included measuring antibodies in sera, testing a subset of respiratory samples for COVID-19 using RT-PCR and antigen tests, and measuring Hemoglobin, CRP, Vitamin D, and zinc in Round 1. Results Participants showed 23% (95% CI 21.9-24.5) antibody seroprevalence in round 1, increasing across rounds to 29% (95% CI 27.4-30.6), 49% (95% CI 47.2-50.9) and 79% (95% CI 77.4-80.8). Urban residents had 2.6 times (95% CI 1.9-3.6) higher odds of seropositivity than rural residents. Seropositivity did not differ between genders. Individuals aged 20-49 had 7.5 (95% CI 4.6-12.4) times higher odds of seropositivity compared to children aged 0-4. Most participants were asymptomatic, with no reported mortality. Vitamin D deficiency was linked to seroprevalence. COVID-19 was confirmed in 1.8% of individuals via RT-PCR and antigen tests. Conclusions: The data suggests a steady increase in humoral immunity in Pakistan, likely due to increased transmission and potential cross-protective immunity, which may be associated with asymptomatic disease, leading to the reduction of morbidity and mortality observed.

This study investigates the microbial composition of a commercially available Swiss fermented milk and colostrum product with a history of use in chronic condition management since 2014. The analysis, performed using the Axiom Microbiome Array, identified a high number of targets corresponding to microbial species classified as probiotics belonging to the Bifidobacteriaceae family. The array provided 28 unique targets, each corresponding to a specific microbe. Next, the amino acid sequences of beta-galactosidase and sialidase from Bifidobacteria and humans were studied because these enzymes are responsible for the production of GcMAF (Gc protein-derived Macrophage Activating Factor) from the Gc protein that is abundant in colostrum. The Bifidobacterial enzymes showed striking functional similarities with their human counterparts. In addition, the study explores the potential health benefits of this product with a focus on GcMAF and chondroitin sulfate, a glycosaminoglycan highly represented in milk and colostrum. The high concentration of specific Bifidobacteria strains contributes to these benefits through two mechanisms: enhanced GcMAF production and activation of chondroitin sulfate, which in turn exhibits GcMAF-like activity. These findings suggest that the Bifidobacteria-rich Swiss product could offer health benefits through these combined mechanisms.

the close phylogenetic relationship between ascidians (Tunicata) and vertebrates makes them a powerful model for studying the innate immune system. To better understand the nature and dynamics of immune responses and the mechanisms through which bacterial infections are detected and translated into inflammation in Ciona robusta, we applied an approach combining in vivo lipopolysaccharide (LPS) stimulation, immune-labelling and functional enzymatic analyses. The immunohistochemistry showed that toll-like receptor 4 (TLR4) and nuclear factor kappa B (NFκB) were expressed during the inflammatory pharynx response 4 hours post-LPS, with formation of immune-stained haemocyte nodules in the vessel lumen. Pharynx vessel endothelium also took part in the inflammatory response. Observations of histological sections from naive and MS-inoculated ascidians confirmed immuno-positive tissue response. Enzyme immune parameters – which included the activity of phenoloxidase, glutathione peroxidase, lysozyme, alkaline phosphatase and esterase – showed up-modulation 4 hours after LPS injection, confirming their involvement during ascidian inflammatory response. These findings provide new insights into the mechanisms involved in LPS-induced C. robusta response and suggest that a broad innate immune mechanism is involved in the regulation of tunicate inflammatory responses.

Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently reg-ulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic al-terations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was up-regulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced anti-gen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production.

Cellular Integrated Stress Response (ISR), the mitochondrial Unfolded Protein Response (UP-Rmt) and the IFN signaling are associated with viral infections. The Activating transcription fac-tor 4 (ATF4) plays a pivotal role in these pathways and controls the expression of many genes involved in redox processes, amino acid metabolism, protein misfolding, autophagy and apop-tosis. The precise role of ATF4 during viral infection is unclear and depends on cell hosts, viral agents and models. Furthermore, ATF4 signaling can be hijacked by pathogens to favor viral in-fection and replication. In this review, we summarize the ATF4-mediated signaling pathways in response to viral infections, focusing on human immunodeficiency virus (HIV). We examine the consequences of ATF4 activation for HIV replication and reactivation. The role of ATF4 in au-tophagy and apoptosis is explored as in the context of HIV infection programmed cell deaths contribute to the depletion of CD4 T cells. Furthermore, ATF4 can also participate in the estab-lishment of innate and adaptive immunity that are essential for the host to control viral infec-tions. We finally discuss the putative role of the ATF4 paralogue, named ATF5, in HIV infection. This review underlines the role of ATF4 at the crossroads of multiple processes reflecting host-pathogen interactions.

Abstract: Malaria transmission intensity affects the development of naturally acquired immunity to malaria. An absolute correlate of protection against malaria is lacking. However, anti-body-mediated functions against P. falciparum correlate with protection against malaria. In children, antibody-mediated functions against P. falciparum generally decline with a reduction in exposure; however, it is unclear whether adults maintain antibody-mediated functions in the context of re-duced exposure. This study assessed antibody-dependent respiratory burst (ADRB) in individuals from an area with declining malaria transmission. In an age-matched analysis, we compare ADRB activity during high versus low malaria transmission periods. Age significantly predicted higher ADRB activity in both the high and low malaria transmission periods. Within all age categories, ADRB activity was higher during the high compared to the low malaria transmission period, with only the adults during the high malaria transmission period having their mean ADRB activity above the ADRB cut-off. Interestingly, ongoing P. falciparum infection influenced ADRB activity during the low but not the high malaria transmission period. These findings propose that naturally acquired immunity to P. falciparum is affected in children and adults as malaria transmission declines, im-plying that vaccines will be necessary to induce and maintain protection against malaria.

Babesia microti (B. microti), is a tick-transmitted protozoan parasite that infects red blood cells. It is the primary cause of human babesiosis in the US. It is also considered an emerging pathogen that continues to expand in terms of both numbers of cases and geograpical range. The severity of babesiosis can range from asymptomatic to fatal. Nevertheless, the mechanisms important for resolution of infection versus pathology remain largely unknown. In the current study we used a mouse model to evaluate factors important in protection from reinfection with B. microti following the clearance of a primary infection. Both B cell and CD4 T cell deficient mice failed to completely eliminate parasitemia 36 days post-infection following primary challenge. In the recall mouse model of infection, wild type or specific gene deleted mice were reinfected with the same strain of B. microti parasites 30-36 days after the initital primary infection, and the development of parasitemia was evaluated. Our results show that wild type mice were protected from reinfection with B. microti. In contrast, B cell and CD4 T cell deficient mice were only modestly impaired in their ability to protect against rechallenge as protection was more similar to reinfected wild type mice than naïve mice. However, one reinfected B cell deficient mice developed parasitemia levels similar to those observed in primary infection. Other factors including IFN-γ, inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88 important for signling via IL-18 and IL-1 had no effect on rechallenge. Thus our study shows that infection with B. microti confers at least short term protection against rechallenge with the same parasite strain. Our data show that CD4 T cells make an important contribution to both primary and rechallenge infection with B. microti. They also suggest that antibody might play an important role in protection against reinfection or persistent infection. However, overall our results Our results suggest that no one aspect of the immune system is solely responsible for adequate protection against reinfection with B. microti.

Recent research has unveiled intriguing insights suggesting that the body's immune system may be implicated in Parkinson's disease (PD) development. Studies have observed disparities in pro-inflammatory and anti-inflammatory markers between PD patients and healthy individuals. This finding underscores the potential influence of immune system dysfunction in the genesis of this condition. A dysfunctional immune system can serve as a primary catalyst for systemic in-flammation in the body, which may contribute to the emergence of various brain disorders. The identification of several genes associated with PD, as well as their connection to neuroinflamma-tion, raises the likelihood of disease susceptibility. Moreover, advancing age and mitochondrial dysfunction can weaken the immune system, potentially implicating them in the onset of the dis-ease, particularly among older individuals. Compromised integrity of the blood-brain barrier could facilitate the immune system's access to brain tissue. This exposure may lead to encounters with native antigens or infections, potentially triggering an autoimmune response. Furthermore, there is mounting evidence supporting the notion that gut dysbiosis might represent an initial trigger for brain inflammation, ultimately promoting neurodegeneration. In this comprehensive review, we will delve into the numerous hypotheses surrounding the role of both innate and adaptive immunity in PD.

ABSTRACT: The idea of a Common Mucosal Immune system (CMS) is 50 years old. Its relevance to immune protection at mucosal sites and its potential to modulate the impact of vaccination-induced protection against infection of the airway, has been poorly understood. The consequent failure of current SARS-CoV-2 vaccination to satisfy expectations with respect to prevention of infection, viral transmission, duration of protection and pattern of clinical protection, led to public health and medical decisions now under review. This review summarises knowledge of the CMS in man, including the powerful role it plays in immune protection and lessons with respect to what can and can not be achieved by systemic and mucosal vaccination for prevention of airway infection. The powerful impact in both health and disease of optimising delivery of immune protection using selected isolates from the respiratory microbiome, is demonstrated through review of randomised controlled trials (RCT’s) in subjects with chronic airway disease, and in otherwise healthy individuals with risk factors, in whom the idea of mucosal immune resilience is introduced.

Abstract: OTUD6A is a deubiquitinase that plays crucial roles in various human diseases. However, the precise regulatory mechanism of OTUD6A remains unclear. In this study, we found that OTUD6A significantly inhibited the production of type I interferon. Consistently, peritoneal macrophages and bone marrow-derived macrophages from Otud6a^-/- mice produced more type I interferon after virus infection compared to cells from WT mice. Otud6a^-/- mice also exhibited increased resistance to lethal HSV-1 and VSV infections, as well as LPS attack due to decreased inflammatory responses. Mechanistically, mass spectrometry results revealed that UBC13 was an OTUD6A-interacting protein, and the interaction significantly enhanced after HSV-1 stimulation. Taken together, our findings suggest that OTUD6A plays a crucial role in the innate immune response and may serve as a potential therapeutic target for infectious disease.

The plant immunity system is more and more revisited and new elements and roles are attributed to participate in the response to biotic stress. New terminology is also applied trying to identify different players in the whole scenario of immunity: Phytocytokines are one of those elements that are gaining more attention due the characteristics of processing and perception, and showing they are part of a big family of compounds that can amplify the immune response. This review aims to highlight the last findings about the role of phytocytokines in the whole immune response on biotic stress, including basal and adaptive immunity, and to expose the complexity in their action in plant perception and signaling events.

Autism Spectrum Disorders (ASD) are neurodevelopmental disturbances affecting social skills, whose incidence worldwide is dramatically increasing. Together with the rise of ASD prevalence, several immune conditions are following the same trend, including Atopic Dermatitis (AD), with a possible clinical relationship with ASD. To date, their pathogenesis is still unknown, but several studies highlighted the relevance of gene-environment interactions to the onset of both disorders. Among potential contributing factors, microRNAs (miRNAs), small molecules capable of controlling gene expression and targeting mRNA transcripts, might represent one of the major circulating link, unraveling the connections between neurodevelopmental and immune conditions. We conducted a systematic literature review, under the PRISMA guidelines, trying to define the panel of common miRNAs involved in both ASD and AD. The review retrieved articles published until December 13, 2018, in PubMed, ScienceDirect, PsycARTICLES and Google Scholar. We found a handful works dealing with miRNAs in ASD and AD, with the most overlapping dysregulated miRNAs being miR-146 and miR-155. Two possible compounds are abnormally regulated in both ASD and AD subjects, possibly cross-contributing to the interactions between the two disorders, setting the basis to investigate more precisely the possible link between ASD and AD from another, not just clinical, perspective.

Using a randomized, crossover approach, cyclists (N = 20, overnight fasted) engaged in three 75-km time trials while ingesting water (WAT) or carbohydrate (0.2 g/kg every 15 minutes) from bananas (BAN) or a 6% sugar beverage (SUG). Blood samples were collected pre-exercise and 0 h-, 1.5 h-, and 21 h-post-exercise, and analyzed for NK cytotoxicity activity (NKCA) using pure NK cell populations. The two carbohydrate trials (BAN, SUG) compared to WAT were associated with higher post-exercise glucose, and lower cortisol, total blood leukocyte, neutrophil, and NK cell counts (interaction effects, P < 0.001). The immediate post-exercise increase in NK cell counts was higher in WAT (78%) compared to BAN (32%) and SUG (15%) trials (P ≤ 0.017). The 1.5 h post-exercise decrease in NK cell counts did not differ after WAT (−46%), BAN (−46%), and SUG (−51%) trials. The pattern of change in post-exercise NKCA differed between trials (P < 0.001). The 1.5 h post-exercise decreases in NKCA were 23%, 29%, and 33% in the WAT, BAN, and SUG trials, respectively, but trial contrasts did not differ significantly. Carbohydrate ingestion from BAN or SUG attenuated immediate-post-exercise increases in leukocyte, neutrophil, and NK cell counts, but did not counter the 1.5-h decreases in NK cell counts and NKCA.

Introduction: The top priority of active immunoprophylaxis of pertussis is immunisation of infants as they can develop severe multiple-organ complications or even die from this disease. Objectives: The aim of the work is the identification of factors negatively affecting vaccine immunity to pertussis in preschool children prior to the administration of the first booster. Patients and Methods: The research was conducted on 352 children from 4.5 to 5.9 years of age who were hospitalised in the University Children’s Hospital in Lublin (Poland) from 1 January 2012 to 31 December 2015. The children taking part in the study had been administered all the mandatory vaccines from their birth to the age of 2 or 2.5 years old according to the Polish Immunisation Program 2008-2009. The immunoenzymatic method ELISA was applied to assess vaccine immunity to tetanus, diphtheria, pertussis, Haemophilus influenzae type b (Hib), poliomyelitis (IPV), mumps, rubella and measles. The level of vaccine antibodies to hepatitis type B was determined chemilumiscently. Results: The protective antibody titer was not found in 41 (11.65%) children before the administration of the booster. To verify the collective impact of parameters analised on antibody titer to pertussis, the Generalized Linear Model (GLZ) was used. Gender, type of vaccine, asthma, Hib and mumps antibody titers have been shown to be predicators of vaccine immunity to pertussis. Conclusions: Immunomodulation considered on the example of titer of IgG antibody to pertussis can serve as a useful model of the assessment of development of acquired immunity after mandatory vaccinations.

Malaria comprises a spectrum of disease syndromes and the immune system is a major participant in malarial disease. This is particularly true in relation to the immune responses elicited against blood stages of Plasmodium-parasites that are responsible for the pathogenesis of infection. Mouse models of malaria are commonly used to dissect the immune mechanisms underlying disease. While no one mouse model of Plasmodium infection completely recapitulates all the features of malaria in humans, collectively the existing models are invaluable for defining the events that lead to the immunopathogenesis of malaria. Here we review the different mouse models of Plasmodium infection that are available, and highlight some of the main contributions these models have made with regards to identifying immune mechanisms of parasite control and the immunopathogenesis of malaria.

This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19. There are good reasons to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID- 19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background of this hypothesis based on lungs and intestine relationships.

Maternal infectious disease may pose considerable challenges to the fetal health due to the distribution of important elements of the sanguine and lymphatic system from the mother via the umbilical cord. The mother and the fetus have a degree of interdependence that is similar to the one between the eukaryotic cell and the mitochondrion, particularly during the first half term of the pregnancy, which explains the increased appetite of the expecting mother during the first stages of the fetal development. There is a solid bridge between the adaptive immune system and the encephalon that was only discovered a few decades ago. As a result, scientists may still be in the introductory stages of research, and there might be a significant and profound degree of association between the immune system and a healthy neurological development. There is a significant link between the onset of significant maternal infectious disease and the onset of neurodevelopmental disease in the fetus, and virtually all immune cells play major roles in the promotion and inhibition of neurogenesis alike. Likewise, there is a probability that maternal infectious diseases during pregnancy represent a risk factor of fetal neurodevelopmental disease, as a pressurised development of the adaptive immune memory could result in a pressurised or inhibited neurological development, which both can result in a delayed development of certain sub-regions of the brain. For example, the fetus may display poorer social abilities and sharp analytical skills later in life, which is an important sign of neurodevelopmental disease. A pressurised development of the adaptive immune memory could not require the development of a significant form of disease, but rather just a sharp rate of immune preparation against several important pathogenic agents during the introductory stages of life, when the encephalon experiences the sharpest increase rate in development. The problem per se is not the process of immunisation, but a much sharper process of immunisation over the first stages of life in case of an exposure to one dangerous pathogen or more numerous kinds of pathogens and antigens that normally cause moderate disease morbidity. The more dangerous the microbe is, the sharper the development of the adaptive immune memory will be, and the same happens in the case of an increased number of infectious microbes and antigens that infected the cells of the mothers and the fetuses in cause, and this may, in the majority of the situations, still be the case even if the pathogens are already significantly weakened or lifeless, given that the gain of adaptive immune memory alone constitutes an important factor of neurogenesis and an increased rate of neurological development, and that the infant will become almost or fully protected against the pathogens in cause, despite not having had experienced the disease beforehand. In this case, neurodevelopmental delays are possibly not caused by an impaired neurogenesis, but by an excessive one, whilst maternal infection-associated neurodevelopmental delays may be caused by an impaired neurogenesis. Nevertheless, the aetiology of immunity-related neurodevelopmental delays may be more complex in nature and implicate a chronological and spatial sequence of induced excedentary and deficitary rates of neurogenesis, hence reflecting the incredibly complex nature and various forms of neurodevelopmental disease. It is important to mention that a single dose of infant immunisation brings significantly lower risks of adverse neurological events than the onset of a significant maternal infectious disease during pregnancy. The objective of paediatric neuro-immunological studies may be to improve the understanding of the association between a healthy immune developmental rate and a balanced ratio of the developmental rates of important brain regions and sub-regions.

Rapid development and deployment of vaccines greatly reduced mortality and morbidity during the COVID-19 pandemic. The most widely used COVID-19 vaccines approved by national regulatory authorities require intramuscular administration. SARS-CoV-2 initially infects the upper respiratory tract where the infection can be eliminated with little or no symptoms by an effective immune response. Failure to eliminate SARS-CoV-2 in the upper respiratory tract results in lower respiratory tract infections that can lead to severe disease and death. Presently used intramuscularly administered COVID-19 vaccines are effective in reducing severe disease and mortality but are not entirely able to prevent asymptomatic and mild infections as well as person to person transmission of the virus. Individual and population differences also influence susceptibility to infection and the propensity to develop severe disease. This article provides a perspective on the nature and the mode of delivery COVID-19 vaccines that can optimize protective immunity in the upper respiratory tract to reduce infections and virus transmission as well as severe disease.

: Cytokine storm is usually described as one of the main reasons behind COVID-associated mor-tality. Cytokines are essential protein molecules engaged in immune responses; they play a critical role in protection against infections. However, they also contribute to inflammatory reactions and tissue damage, becoming a double-edged sword in the context of COVID-19. Recent studies have suggested various cytokines and chemokines that play a crucial role in the immune response to SARS-CoV-2 infection. One such cytokine is Interleukin 27 (IL-27), which has been found to be elevated in the blood plasma of patients with COVID-19. Within this study, we will explore the role of IL-27 in immune responses and address our own findings concerning this cytokine in COVID-19. It affects a wide variety of immune cells; regardless of the pathological process it is involved in, IL-27 is critical for upholding the necessary balance between tissue damage and cytotoxicity against in-fectious agents and/or tumors. In COVID-19, it is involved in multiple processes, including antiviral cytotoxicity via CD8+ cells, IgG subclass switching, and even the activation of Tregs.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine and oncology applications, Ad based platforms offer advantages including ease of genetic manipulation, scale of production and well established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that may need to be overcome for adenovirus based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects upon the downstream impact of an adenovirus-based therapeutic. This review focusses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, both in context of the innate and adaptive immune responses. We summarize different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

Microbicides, topical antiseptic agents, and a revolutionary advance in HIV prevention aim to prevent the entry of infectious agents into the human body, thus stopping the sexual transmission of HIV and other sexually transmitted diseases. Microbicides represent the promise of a new age in preventive measures against one of the world's most pressing health challenges. In addition to their direct antiviral effects during HIV transmission, microbicides also influence vaginal mucosal immunity. This article reviews microbicides by presenting different drug classifications and highlighting significant representatives from each group. It also explains their mechanisms of action and presents information about vaginal mucosal immune responses, emphasizing the critical role they play in responding to HIV during sexual transmission. For each chemical compound, the article provides a brief overview of relevant preclinical and clinical research, emphasizing their potential as microbicides.The article offers insights into the multifaceted impact of microbicides, which signify a pivotal step forward in the pursuit of effective and accessible pre-exposure prophylaxis (PrEP).

The aim of this study was to evaluate whether alterations in food availability compromise the metabolic homeostasis of honey bees exposed to three fungicides alone or together. Ten honey bee colonies were utilized, with half receiving energy-protein supplementation for 15 weeks while another five colonies had their protein supply reduced with pollen traps. Subsequently, forager bees were collected and exposed by contact to 1 or 7 µg of bixafen, prothioconazole, and trifloxystrobin, either individually or in combination. After 48 hours, abdomens without the intestine was used for the analysis of expression of antioxidant genes (SOD-1, CAT, and GPX-1), detoxification genes (GST-1 and CYP306A1), the storage protein gene vitellogenin, and immune system antimicrobial peptide genes (Defensin-1, Abaecin, Hymenoptaecin, and Apidaecin), through real-time PCR. All pesticide treatments induced changes in gene expression, with bixafen showing the most prominent upregulation. Exposure to 1 µg of each of the three pesticides resulted in upregulation of genes associated with detoxification and nutrition processes, and downregulation of immune system genes. When the three pesticides were combined at a dose of 7 µg each, there was a pronounced downregulation of all genes. Dietary supplementation led to a slight reduction in gene expression alterations provoked by the fungicides.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host and the possible outcomes of host-pathogen interaction.

Here, we found higher percentage of CD8+ T cells in piglets immunized with CVC1302-adjuvanted inactivated FMDV vaccine. We wonder whether promoted cellular immunity induced by CVC1302-adjuvanted inactivated FMDV vaccine due to the promoted antigen cross-presentation efficiency of OVA by DC mainly via the cytosolic pathways, demonstrated by enhanced levels of lysosomal escape of OVA in DC, loaded with OVA and CVC1302. Higher levels of ROS and significant enhanced elevated lysosomal pH in DC facilitated the lysosomal escape of OVA. Significant enhanced CTL activities were observed in mice immunized with OVA-CVC1302. Overall, CVC1302 increased the cross-presentation of exogenous antigens and the cross-priming of CD8+ T cells by alkalizing the lysosomal pH and facilitating the lysosomal escape of antigen. These studies shed new light on the development of immunopotentiators to improve the cellular immunity induced by vaccine.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

The rapid introduction of DAAs has revolutionized the treatment of chronic HCV infection, however some concerns have been arose about their early and long term safety in real life settings. Therefore, these drugs achieve a robust and sustained virological response in a short duration of treatment, being a quick winning option, but, what then? At now an extensive follow-up in real life settings does not exist particularly on HCC occurrence as recently suggested in a Cochrane review . In this regard from February 2015 to December 2017 a group of 5 Hospital and Academic Centers in Southern Italy (Campania Region) managed an observational, prospective, real-life study on efficacy and safety of DAAs treatment schedule enrolling 1022 consecutive HCV patients treated with IFN-free DAAs regimens being followed-up for 24 months. Our preliminary data on the first 360 patients out of 1022 whose completed at least 66 weeks follow-up, based on clinical, laboratory and expert ultrasonography every three months, showed an SVR in 342 out 360 (95%) patients of which 9 had a new diagnosed HCC (2.63%). Specifically HCC developed in mean after 16,2 months after end of treatment as one or more nodules (2-3 cm in mean) with an increase in alpha-fetoprotein 10 x u.n.v (n.v. <15 UI/mL) in patients with F4 fibrosis staging at the time of treatment enrolment. In conclusion, in view of our findings and literature evidences, regular clinical, laboratory and expert ultrasonography follow-up should carefully performed also on these patients and the current Faster, Higher, Stronger approach to the new antivirals development should strongly be revisited in the light of possible late adverse events like HCC occurrence and the relative economic impact on health care system cost.

We advance the notion that much, like artificial nanoparticles, relatively more complex biological entities with nanometric dimensions such as pathogens (viruses, bacteria and other microorganisms) may also acquire a biomolecular corona, upon entering the blood circulation of an organism. We view this biomolecular corona as a component of a much broader non-cellular blood interactome that can be highly specific to the organism, akin to components of the innate immune response to an invading pathogen. We review published supporting data and generalize these notions from artificial nanoparticles to viruses and bacteria. Characterization of the non-cellular blood interactome of an organism may help explain apparent differences in the susceptibility to pathogens among individuals. The non-cellular blood interactome is a candidate therapeutic target to treat infectious and non-infectious conditions.

Accurate data on susceptibility rates against measles in general population of Greece are scarce. Many studies estimate the vaccination coverage but none has calculated the nationwide immunity rate, involving all age groups, against measles virus. The purpose of our study was to determine the immunity status to measles, especially after the latest outbreak in 2017-2018. In total, 3,972 leftover blood samples were collected from a nationwide laboratory network using a geograph-ically stratified sampling strategy and were tested for the presence of measles specific IgG anti-bodies. The overall crude seroprevalence was calculated 89.6% and the adjusted 89.8% (95% CI: 88.8% - 90.8%). There was no statistically significant difference in seropositivity among sexes (p=0.783). Higher immunity rates and antibody titer were found in older age groups ≥ 41 years old (94.9%, 95% CI: 93.7% - 95.9%, and 730.0 IU/l) in comparison to younger individuals 1-40 years old (83.4%, 95% CI: 81.6% - 85.7%, and 616.5 IU/l). ). Comparing the seroprevalence among Nomenclature of Territorial Units for Statistics (NUTS 2), a statistically significant difference was estimated among them (<0.001). The two regions where higher measles incidence was observed during the 2017-2018 outbreak, Eastern Macedonia and Thrace and Western Greece, were among the four regions with the lower seropositivity (84.6%, 95% CI: 79.9% -89.4% and 85.9%, 95% CI: 81.4% - 90.4%, respectively). Our study showed a measles immunity gap that affects younger age groups and makes a new measles outbreak likely. Enforcement of vaccination campaigns and ad-dressing vaccine hesitancy could bridge it and achieve the required target for herd immunity.

Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye´s immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system’s main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.

The practice of physical activity is an effective non-pharmacological strategy for preventing and treating chronic diseases. A large body of evidence has contributed to establishing a positive correlation between a physically active lifestyle and health benefits, including enhanced vaccination responses, lower numbers of senescent T-cells, increased T-cell proliferative capacity, lower levels of inflammatory cytokines, and improved neutrophil and macrophage function. While females are generally thought to exert more robust immune responses than males in response to a variety of challenges, and both male and female sex hormones have been suggested as mediators of immune function, research on this topic has not always been designed with a sex-specific lens. The goal of this review is to summarize the available experimental and clinical evidence linking exercise and immune function in male and female subjects, with an emphasis on sex differences and sex-specific mechanisms. Overall, the available evidence indicates that moderate exercise and physical activity improves immune function in both sexes, whereas prolonged and high-intensity exercise temporarily impairs immune responses at a higher degree in females. A role of male and female sex hormones in these sex-specific effects is also discussed.

Verticillium wilt (VW) is a soil borne fungal diseases caused by Verticillium dahliae Kleb, and lead to serious damage to cotton production annually in the world. In our previous study, a transmembrane protein 214 protein (TMEM214) gene associated with VW resistance was map-based cloned from Gossypium barbadense (G. barbadense). TMEM214 proteins are a kind of transmembrane protein, but their function in plants is rarely studied. To reveal the function of TMEM214s in VW resistance, all six TMEM214s were cloned from G. barbadense in this study. These genes were named as GbTMEM214-1, GbTMEM214-4 and GbTMEM214-7 according to their location on the chromosomes, and the encoded proteins are all located on cell membrane. TMEM214 genes were all induced by Verticillium dahliae inoculation and showed significant differences between resistant and susceptible varieties, but the expression patterns of GbTMEM214s under different hormone treatments were significantly different. Virus-induced gene silencing analysis showed the resistance to VW of GbTMEM214s-silenced lines decreased significantly, which further proves the important role of GbTMEM214s in the resistance to Verticillium dahliae. Our study provides an insight into the involvement of GbTMEM214s in VW resistance, which was helpful to better understand the disease resistance mechanism of plants.

Tilapia lake virus (TiLV), a major pathogen of farmed tilapia, is known to be vertically transmitted. Here, we hypothesize that Nile tilapia (Oreochromis niloticus) broodstock immunized with a TiLV inactivated vaccine can mount a protective antibody response and passively transfer maternal antibodies to their fertilized eggs and larvae. To test this hypothesis, three groups of tilapia broodstock, each containing 4 males and 8 females, were immunized with either a heat-killed TiLV vaccine (HKV), a formalin-killed TiLV vaccine (FKV) (both administered at 3.6 ×106 TCID50 per fish), or with L15 medium. Booster vaccination with the same vaccines was given 3-weeks later, and mating took place 1 week thereafter. Broodstock blood sera, fertilized eggs and larvae were collected from 6-14 weeks post-primary vaccination for measurement of TiLV-specific antibody (anti-TiLV IgM) levels. In parallel, passive immunization using sera from the immunized female broodstock was administered to naïve tilapia juveniles to assess if antibodies induced in immunized broodstock were protective. The results showed that anti-TiLV IgM was produced in the majority of both male and female broodstock vaccinated with either the HKV or FKV and that and that these antibodies could be detected in the fertilized eggs and larvae from vaccinated broodstock. Higher levels of maternal antibody were observed in fertilized eggs from broodstock vaccinated with HKV than those vaccinated with FKV. Low levels of TiLV-IgM were detected in some of the 1-3-day old larvae but were undetectable in 7-14-day old larvae from the vaccinated broodstock, indicating a short persistence of TiLV-IgM in larvae. Moreover, passive immunization proved that antibodies elicited by TiLV vaccination were able to confer 85% to 90% protection against TiLV challenge in naïve juvenile tilapia. In conclusion, immunization of tilapia broodstock with TiLV vaccines could be a potential strategy for the prevention of TiLV in tilapia fertilized eggs and larvae, with HKV appearing to be more promising than FKV for maternal vaccination.

The purpose of this study was to see how dietary supplementation with phenylpyruvate affected broiler chicken growth, slaughter performance, gut health microbiota, and immunity. A total of 288 day old broiler chickens were randomly assigned to one of four groups (6 replicates each with 12 chicken). NC (basal diet), PC (basal diet plus antibiotic virginiamycin 15ppm), LCP and HCP (basal diet plus phenylpyruvate 1kg/t and 2kg/t, respectively). Results showed that PC had higher ADFI during the first 21 days, and better FCR than the NC, the LCP and HCP also improved broilers’ FCR 0.001 and 0.037% in relation to NC respectively. HCP has a higher all-eviscerated ratio than NC and less abdominal fat than LCP. HCP has increased villus length and crypt depth in the ileum compared to the NC. Bursa was lower in HCP and thymus was lower in LCP and PC. In contrast HCP have lower pro-inflammatory cytokine IL-1, as well as lower TLR4. The phenylpyruvate improved family Selenomonadaceae, genus Megamonas Bacteroides species that are known for beneficial effects like for maintenance of the cell surface structure, regulating aromatic amino acids and C. jejuni-suppressive treatment respectively. Finally, phenylpyruvate feed supplement can be utilized to improve growth performance and positively modulate gut microbiota, however this is less efficient than antibiotics in improving growth performance, although more efficient in improving productive performance and gut morphology. Moreover, high dose of phenylpyruvate is more effective than low dose

In this article we have presented a new perception of herd immunity threshold (HIT) which considers that only a “band of population” are susceptible to any pathogenic infection. This is termed as the “effective herd immunity threshold” (EHIT) and the progression of the disease (caused by this pathogenic infection) is mainly determined by this EHIT value. We have argued here that this EHIT value (considering the immunity band picture in the population) will be substantially lower than the estimated canonical HIT values obtained from various existing models. We propose that the actual prediction of the disease progression should now be calculated using the EHIT values.

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.

The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.

Tricarboxylic acid cycle (TCA) is a series of chemical reactions in aerobic organisms used to generate energy via the oxidation of acetyl-CoA derived from carbohydrates, fatty acids, and proteins. In the eukaryotic system, the TCA cycle completely occurs in mitochondria, while the intermediates of the TCA cycle are retained in mitochondria due to their polarity and hydrophilicity. Under conditions of cell stress, mitochondria become disrupted and release their contents, which act as danger signals in the cytosol. Of note, the TCA cycle intermediates may also leak from dysfunctioning mitochondria and regulate cellular processes. Increasing evidence shows that the metabolites of the TCA cycle are substantially involved in the regulation of immune responses. In this review, we aimed to provide a comprehensive systematic overview of the molecular mechanisms of each TCA cycle intermediate that may play key roles in regulating cellular immunity in cell stress and discuss their implications for immune activation and suppression.

Coccidiosis remains a major disease and economic challenge for the global poultry industry. Coccidiosis in chickens is caused by seven Eimeria species that target specific regions of the gastrointestinal tract and cause malabsorptive or haemorrhagic disease. These Eimeria species infect segment-specific epithelial cells and thus need to navigate the host’s indigenous microbiome and intestinal defences to establish an infection and cause disease. Good husbandry practices, prophylactic use of anticoccidial drugs and/or live parasite vaccination have been the primary control measures employed but there are challenges with vaccination and growing constraints on anticoccidial drug use. This review, therefore, considers available information on the key steps of the infection process, notable microbiome- or host-related changes occurring, and the (potential) influence of dietary ‘alternatives’ to anticoccidial drugs. There is good available evidence to indicate that some phytogenics, prebiotics, probiotics, betaine, n-3 fatty acids, as well as carbohydrase enzymes and anti-IL-10 antibodies, can (beneficially) modulate at least some of these features in coccidiosis-specific challenge studies. As a minimum, these anticoccidial drug ‘alternatives’ could support the establishment of a desirable host microbiome and optimum immune system development. It is important to better understand the potential of these ‘alternatives’ in commercial production and how they can complement, or reduce, the use of anticoccidial drugs.

Although Mast cells are known as key drivers of type I allergic reactions, there is increasing evidence for their critical role in host defense. MCs do not only play an important role in initiating innate immune responses, but also influence the onset, kinetic and amplitude of the adaptive arm of immunity, or fine-tune the mode of the adaptive reaction. Intriguingly, MCs have been shown to affect T cell activation by direct interaction or indirectly by modifying properties of antigen-presenting cells, and can even modulate lymph node-borne adaptive responses remotely from the periphery. In this review, we provide a summary of recent findings that explain how MCs act as a link between the innate and the adaptive immunity, all the way from sensing inflammatory insult to orchestrating the final outcome of the immune response.

Many reports showed a dramatic decrease in the levels of physical activity during the current pandemic of SARS-COV-2. This has substantial immunometabolic implications, especially in those at risk or with metabolic diseases including individuals with obesity and Type 2 diabetes. Here we discuss the route from physical inactivity to immnometabolic aberrancies; focusing on how insulin resistance could represent an adaptive mechanism to the low physical activity levels and/or high energy intake and on how such an adaptive mechanism could derail to be a pathognomonic feature of metabolic diseases creating a vicious circle of immune and metabolic aberrancies. We provide a theoretical framework to the severe immunopathology of COVID-19 in patients with metabolic diseases. We finally discuss the idea of exercise as a potential adjuvant against COVID-19 and emphasize how even interrupting prolonged periods of sitting with short time breaks of very light activity could be a feasible strategy to limit the deleterious effects of sedentary behavior.

One of the biggest demanding situations for food security in the 21^st century is to enhance crop yield stability through the improvement of diseases-resistant crops. Managing plant health is a major challenge for modern food production and compounded by the lack of common ground among the many disease control disciplines involved. All plants simultaneously engage with billions of microbes which can be collectively referred to as the plant microbiome. Most microbes inside the plant microbiome are harmless or even beneficial to the plant as they promote plant growth or provide protection in opposition to diseases. However, some of these microbes also cause disease with devastating effects on crop yields. To prevent pathogen infection, plants have evolved an advanced innate immune system that recognizes conserved cell surface molecules that most pathogen possesses. Activation of the plant immune system stops the invading pathogen, however this comes with fitness cost that significantly reduces plant growth and leads to yield penalty. Apart from their innate immune system controlling pre-programmed defense reactions, plants can also increase the responsiveness of their immune system in response to selected environmental signals. This phenomenon is known as “defense priming”. Although defense priming rarely provides full protection, its broad-spectrum effectiveness, low-fitness cost, long‐lasting durability and inherited to future generations make it attractive for sustainable crop protection.

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

Background. The course of the COVID-19 epidemic process depends on population immunity which prevents pathogen spread among the population. Aim: to study the evolution of SARS-CoV-2 humoral immunity in the Belarusian population relative to COVID-19 pandemic dynamics. Materials and methods. The work was carried out according to a methodology for assessing population immunity developed by Rospotrebnadzor (Russia) and the Belarusian Ministry of Health with the participation of the St. Petersburg Pasteur Institute (SPPI), taking into account WHO recommendations. The study was approved by the Bioethics Committee of Belarus and the SPPI Bioethics Committee. Participant selection was carried out by questionnaire using a cloud (internet server) service. To monitor population immunity, a cohort of 4,661 people (participating in all stages of seromonitoring) was formed from the overall volunteer group. Volunteers were randomized by age group (1-17, 18-29, 30-39, 40-49, 50-59, 60-69, 70+ years), region, and professional group. For the detection of antibodies (Abs) to nucleocapsid (Nc) and S glycoprotein receptor-binding domain (RBD), corresponding assay systems were used following manufacturer instructions. The study was conducted in 4 stages according to a single scheme. Results. In the 1st stage (pandemic month 15), collective immunity was due mainly to Nc+RBD+ Ab status alone. By the 2nd stage (carried out after 4 months), their share decreased 1.2-fold, while the share of volunteers who had only RBD Abs increased 1.7-fold. In the 3rd and 4th stages (carried out after 9 and 19 months), the share of persons with RBD+Nc‒ compared to the 2nd stage decreased by 3.5%; the proportion of persons with Nc+RBD‒ Abs increased by 1.5-fold. The most important factor in population immunity was vaccination of the population, the coverage of which reached 70% by the 4th stage. Among vaccines, the Sputnik V and Sputnik Light vector designs were used most often. The whole-virion, inactivated BIBP-CorV vaccine was used less often. Conclusion. The evolution of collective SARS-CoV-2 humoral immunity included a set of changes in circulating Ab levels (Nc, RBD). The hybrid immunity formed helped to reduce the incidence to nearly zero.

Keywords: cranberry, exercise, proteomics, oxylipins, gut microbiome, metabolomics, immunity

Feed additive antibiotics have been used for many decades as growth promotors or antibacterial substances world-wide. However, the adverse impacts of using antibiotics in animal or poultry feeds were informed. Therefore, searching for alternatives such as probiotics, prebiotics, phytobiotics, post-biotics, bacteriophages, enzymes, essential oils, or organic acids (OAs) became urgent. The OAs are produced by beneficial intestinal bacteria through the fermentation process of carbohydrates. The OAs and their salts are still used as feed preservatives. They have been long added to feed in order to minimize contamination and growth of harmful bacteria and fungi, reduce the deterioration, as well as prolong the shelf life of feed commodities. Moreover, they have been mostly added to poultry feed as a blend to obtain a maximum beneficial effects. The supplementation of poultry with OAs could improve the growth performance parameters and carcass traits, promote utilization of nutrients, boost the immune response, and inhibit the growth of pathogenic bacteria. Therefore, this review article provides valuable insights into the potential benefits of using OAs-antibiotics alternative in reducing the microbial load, enhancing the performance parameters in broilers and layers, improving the gut heath, as well as boosting of the immune response.

Vaccine hesitancy has emerged as a significant barrier to achieving herd immunity and protecting populations from preventable diseases. Despite the proven effectiveness and safety of vaccines, many individuals remain hesitant or refuse to vaccinate themselves or their children. This review aims to identify the factors contributing to vaccine hesitancy, including misinformation, lack of trust in authorities, cultural beliefs, and access barriers. We also discuss the impact of vaccine hesitancy on public health, including outbreaks of vaccine-preventable diseases and erosion of trust in public health authorities. Furthermore, we present evidence-based communication strategies for addressing vaccine hesitancy, including building trust, providing accurate information, addressing myths and misconceptions, engaging with local influencers, and utilizing social media and digital platforms. By understanding the factors contributing to vaccine hesitancy and implementing effective communication strategies, healthcare providers, public health officials, and community leaders can work towards promoting widespread vaccine acceptance and protecting public health.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

An entomopathogenic nematode, Oscheius tipulae, was isolated from a soil sample. The identification of this species was supported by morphological and molecular markers. The nematode isolate exhibited pathogenicity against different target insects including lepidopteran, coleopteran, and dipteran insects. The virulence of this nematode was similar to that of a well-known entomopathogenic nematode, Steinernema carpocapsae, against the same insect targets. A comparative metagenomics analysis of these two nematode species predicted the existence of a combined total of 272 bacterial species in their intestines, of which 51 bacterial species were shared between the two nematode species. In particular, the common gut bacteria included several entomopathogenic bacteria including Xenorhabdus nematophila, which is known as a symbiotic bacterium to S. carpocapsae. The nematode virulence of O. tipulae to insects was enhanced by an addition of dexamethasone but suppressed by an addition of arachidonic acid, suggesting that the immune defenses of the target insects against the nematode infection is mediated by eicosanoids, which would be manipulated by the symbiotic bacteria of the nematode. Unlike S. carpocapsae, O. tipulae showed high virulence against dipteran insects including fruit flies, onion flies, and mosquitoes. O. tipulae showed particularly high control efficacies against the onion maggot, Delia platura, infesting the Welsh onion in the rhizosphere in both pot and field assays.

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for establishment of serological signatures during vaccination and or infection. We describe here, validation and evaluation of an electro-chemiluminescence (ECL) based Mesoscale Discovery assays (MSD), for estimation of total and functional IgG to SARS-CoV-2 spike, nucleocapsid, and receptor binding (RBD) proteins in human serum samples to establish serological signatures of SARS-CoV-2 natural infection and breakthrough cases. The 9-PLEX assay was validated as per ICH, EMA and US FDA guidelines using a panel of sera samples including the NIBSC/WHO international reference panel (20/268). Assay demonstrated high specificity and selectivity in inhibition assays, wherein the homologous inhibition was more than 85% and heterologous inhibition was below 10 %. Assay also met predetermined acceptance criteria for precision (CV < 30 %), accuracy (70-130 %) and dilutional linearity. Method applicability to serological signatures was demonstrated using sera samples (N=45) representing vaccinated, infected and breakthrough cases. The method was able to establish distinct serological signatures and thus provide potential tool for seroprevalence of SARS-COV-2 during vaccination or infection.

In the past decade, it has been discovered that intestinal flora can influence various organ-specific cancers by altering the body's energy balance, increasing obesity, synthesizing genetic toxins and small signaling molecules, initiating and modulating immune responses, and metabolizing indigestible dietary components, exogenous substances, and drugs. In this review, we will focus on elucidating the role of gut flora based on its molecular mechanisms and its potential therapeutic implications in head and neck tumors in the near future.

The Golgi apparatus, long known for protein processing and vesicular trafficking, has recently emerged as an essential player in innate immune signaling pathways. This review article discusses our growing understanding of Golgi cells' roles in initiating and activating innate immunity pathways. We elaborate on the relevance of membrane connections between Golgi organelles and other organelles such as endoplasmic reticulum, mitochondria, endosomes, and autophagosomes that facilitate efficient access to innate immune signal transduction and subsequent effector responses. Additionally, we discuss microbial strategies that exploit the Golgi while diminishing its associated innate immune responses. By providing greater illumination of its multiple functions and mechanisms of operation, this article offers invaluable insight into how protein processing impacts innate immunity and vice versa.

Poplar (Populus) is a genus of woody plants of value for the pulp industry, green energy, urban landscaping, soil phytoremediation and as an ornamental plant. Due to the increasing economic importance of poplar, there is a need to ensure its stable growth by increasing its resistance to pathogens, as one of the main problems in poplar cultivation is its susceptibility to numerous diseases. Currently, breeding poplars with reduced susceptibility to infections is receiving increasing attention. Genetic engineering can produce organisms with improved traits faster than traditional methods, and with the development of CRISPR/Cas-based genome editing systems, scientists have a new highly efficient tool at their disposal to create valuable genotypes. In this review, we summarize recent research data on poplar diseases, the biology of their pathogens, and how these plants resist pathogens. In the final section, we discuss genetic engineering, genome editing, and microbiome strategies that we believe are suitable for obtaining new improved poplar lines.

The coronavirus disease 2019 (COVID-19) pandemic clearly has had a great influence on the lifestyle of the population, especially on patients with type 2 diabetes mellitus. During the COVID-19 outbreak, many countries/regions implemented social isolation measures, leading to an increase in negative behaviors and impairing the capability of diabetic patients to resist the COVID-19, ultimately causing a severe prognosis. Moreover, multiple studies have emphasized the significance of physical exercise in the management of type 2 diabetic patients infected with COVID-19 as the epidemic progressed. In our study, we selected research focusing on COVID-19-infected diabetic patients from Dec 1, 2019 to Aug 9, 2023 and sought to investigate the impact of type 2 diabetes on the immune function, inflammation factor levels, lung injury and mental disorders of patients, as well as to assess the risk of novel coronavirus pneumonia in these patients. And we also summarized the effects of high-intensity, moderate-intensity and low-intensity exercise on novel coronavirus pneumonia infection in type 2 diabetic patients and the mechanisms of their effects. Finally, diabetic patients with COVID-19 are suggested to perform low-intensity exercise to facilitate their recovery. Our study offers guidance for a proper understanding of the dangers of diabetes and the use of appropriate measures to reduce the risk of novel coronavirus pneumonia infections in type 2 diabetic patients.

Abstract: A multitude of biotic and abiotic stress factors do harm to plants by bringing about diseases and inhibiting normal growth and development. As an omnipotent signaling molecule, salicylic acid (SA) plays crucial roles in plants' tolerance responses to both biotic and abiotic stresses, thereby maintaining plants’ normal growth and improving yields under stresses. In view of this, this paper mainly discusses the role of SA in both biotic stresses, and abiotic stresses of plants. SA regulates the expression of genes involved in defense signaling pathways, thus enhancing plants’ immunity. In addition, SA mitigates the negative effects of abiotic stresses, and acts as a signaling molecule to induce the expression of stress-responsive genes and the synthesis of stress-related proteins. In addition, SA also improves certain yield-related photosynthetic indexes, thereby enhancing crop yield under stresses. On the other hand, SA acts with other signaling molecules in regulating plants’ growth and improving tolerances under stresses. This paper reviews recent advances in SA’s roles in plant stress tolerances, so as to provide theoretical references for further studies concerning the decryption of molecular mechanisms for SA’s roles and the improvement of crop management under stresses.

In this article, we first assessment of peste des petits ruminants (PPR) antibodies in vaccinated pregnant ewes of Kazakh breed fine-fleeced immunized with the PPR vaccine and the duration of maternal immunity in their lambs. Ewes in the last trimester of pregnancy of gestation were immunized with a vaccine from the Nigeria 75/1 strain of the PPR virus (PPRV) produced by the Research Institute of Biological Safety Problems (RIBSP), Kazakhstan. Serum samples from lambs born from vaccinated and unvaccinated ewes were collected a week after birth and at intervals of 7 days for 18 weeks after birth. Serum samples collected from lambs were tested for PPR antibodies using competitive ELISA and Virus neutralization test (VNT). Maternal antibodies (MAs) in lambs born from vaccinated ewes were detected up to 18 weeks with a tendency to decrease starting at week 14 and by the end of the experiment receded below the protective level (&lt;1:8). In the blood serum of a 14-week-old lamb with MAs (1:8), post vaccination with a field dose (103 TCID50) of the vaccine against PPR, the titers of protective antibodies to the PPRV increased to 1:16 on 14 day post vaccination and lamb protected from infection upon field PPRV. A lamb of the same age with MAs in the 1:8 titer was 100% protected from infection with the field PPRV. Therefore, it is recommended that lambs of the Kazakh fine-wool breed be immunized from the age of 14 weeks or older to avoid a period of susceptibility.

Bone Morphogenetic Proteins (BMPs) are a group of structurally and functionally related signaling molecules that comprise a subfamily, belonging to the TGF-β superfamily. Most BMPs play roles in the regulation of embryonic development, stem cell differentiation, tumor growth and some cardiovascular and cerebrovascular diseases. Although evidences are emerging for the antiviral immunity of a few BMPs, more BMPs are needed to determine whether this function is universal. Here we identified the zebrafish bmp4 ortholog, whose expression is up-regulated by challenge with virus or its mimic poly(I:C). Overexpression of bmp4 in EPC cells significantly decreased the viral titer of GCRV-infected cells. Moreover, compared to wild type zebrafish, viral load and mortality were significantly increased in both larvae and adults of bmp4-/- mutant zebrafish infected with GCRV virus. We further demonstrated that Bmp4 promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, thereby inducing the production of type I IFNs in response to virus infection. These data suggest that Bmp4 runs an important role in the host defense against virus infection. Our study expands the understanding of BMP protein functions and opens up new targets for the control of viral infection.

CD4+ T cells orchestrate and regulate immunity within jawed vertebrates, yet our understanding of their evolution, development, and cellular physiology has only begun to be unearthed in the past few decades. Discoveries of genetic diseases that ablate this cellular population have provided insight into their critical functions while transcriptomics, proteomics, and highresolution microscopy have recently revealed new insights into CD4+ T cell anatomy and physiology. This article compiles historical, microscopic, and multi omics data which can be used as a reference atlas to dissect cellular physiology within these influential cells and further understand pathologies like HIV infection that inflict human CD4+ T cells.