Biology and Life Sciences

Abstract: Sepsis and septic shock remain major causes of mortality worldwide, affecting approximately 49 million people annually and accounting for an estimated 11 million deaths, representing nearly 20% of all global deaths. Despite sustained efforts in early diagnosis and treatment, sepsis continues to impose a substantial global health burden. Sepsis is defined as a life-threatening organ dysfunction secondary to a dysregulation of the host response to infection. Despite guidelines-based approaches to its diagnosis and therapy, the mortality rates remain higher even in developed countries, reaching up to 30% in intensive care units. High mortality rates in sepsis are largely driven by clinical heterogeneity, highlighting the critical role of epigenetic modulation mechanisms in shaping diverse clinical phenotypes. The main epigenetic mechanisms that modulate the immune response and outcome in sepsis are: DNA methylation, microRNA synthesis, histone modulation, and RNA methylation. This narrative review examines the role of epigenetic mechanisms in sepsis heterogeneity, phenotyping, management, and outcomes, with particular emphasis on the potential contribution of artificial intelligence to the integration of molecular and clinical data for precision medicine. Consequently, the study of AI-integrated strategies for better tailoring of the diversity of epigenetic changes should be prioritized. Thus, machine learning algorithms, deep learning frameworks, and large language models offer helpful insights in redefining the role of AI in sepsis management from this epigenetic perspective. Despite the support of AI in integrating the epigenetic mechanisms into clinical practice, some disadvantages should be also considered like: black box configuration for deep learning frameworks, inequalities from the past data used for training the models, data privacy, ethical concerns, cohort size, number of parameters considered etc. In conclusion, AI tools represent important means in tailoring the personalized decision tree, especially considering the epigenetic influence on the disease course.

Abstract: Background: Current immunotherapy regimens are phase-agnostic—they treat all patients as if they occupy the same functional immune state, overlooking evidence that the immune system follows an endogenous response program and that the same intervention can produce divergent outcomes depending on when it is administered. Concept: We propose a conceptual framework in which immune responses follow an endogenous phase program driven by the IL-2/Treg axis, manifesting as a continuum of functional immune states operationally approximated as five recurrent phases—tolerance, priming, effector, contraction, and return to tolerance. This program is regulated by the Treg–Tpex balance. We introduce a Conceptual Immune State Landscape (ISL) as a multidimensional heuristic for describing regulatory–effector balance, integrating regulatory capacity, effector potential, and cytokine availability. Key Propositions: (1) Disease context determines the directional bias of immune imbalance (effector-skewed or regulatory-skewed), thereby defining the therapeutic goal. However, the actual biological effect of any intervention is gated by the patient’s current dynamic phase—a principle we term the phase-induced functional switch: the same nominal dose can produce functionally opposite outcomes depending on phase. (2) Combination therapy sequencing should follow the principle of “release suppression first, then amplify response.” (3) Circadian rhythm serves as a superimposed gain control on the endogenous phase program. (4) Therapeutic endpoints should be redefined as system recoverability—the capacity of the immune system to mount a complete response and return to homeostasis—rather than static biomarkers alone. Implications: This framework offers a unified and testable paradigm for optimizing immunotherapy timing, explains contradictory clinical trial results through phase-blind confounding, and generates six specific, falsifiable hypotheses amenable to prospective validation.

Abstract: Artificial intelligence (AI) is rapidly transforming microbiological research by improving pathogen detection, accelerating genomic analysis, enhancing antimicrobial resistance surveillance, and supporting evidence-based public health decision-making. While high-income countries have integrated AI into advanced laboratory systems, many African laboratories continue to face persistent challenges, including inadequate infrastructure, shortages of highly trained personnel, fragmented data systems, unreliable electricity, and limited financial resources. Despite these constraints, several African countries have demonstrated that strategic investments in digital technologies, genomic surveillance, and international scientific collaboration can substantially strengthen microbiology research and laboratory capacity.This article examines the role of artificial intelligence in enhancing microbiology research capacity within low-resource African laboratories through a comparative analysis of empirical experiences across South Africa, Senegal, Nigeria, Kenya, Uganda, the Democratic Republic of the Congo (DRC), and the Central African Republic. Rather than presenting AI as a purely technological innovation, the paper conceptualizes it as an institutional and scientific capacity-building instrument whose effectiveness depends on governance quality, human capital development, infrastructure, and collaborative research ecosystems.Drawing upon recent literature, reports from international organizations, and documented laboratory experiences, the study explores the application of AI in diagnostic microbiology, genomic surveillance, antimicrobial resistance monitoring, digital pathology, and drug discovery. Particular attention is devoted to lessons learned from responses to Ebola virus disease, COVID-19, Mpox, tuberculosis, malaria, and antimicrobial resistance. The analysis demonstrates that AI can significantly improve laboratory efficiency, diagnostic accuracy, outbreak detection, and scientific productivity when supported by appropriate institutional arrangements and sustainable investment.The article identifies persistent barriers that continue to constrain AI adoption, including digital inequality, insufficient laboratory infrastructure, limited computational resources, inadequate regulatory frameworks, data governance concerns, and shortages of multidisciplinary expertise. Building on these findings, the paper proposes an African AI Laboratory Capacity Framework comprising six mutually reinforcing dimensions: infrastructure readiness, human capital development, digital integration, data governance, collaborative research networks, and responsible AI governance.The study concludes that the future of microbiology research in Africa depends not merely on acquiring sophisticated AI technologies but on strengthening resilient scientific institutions capable of integrating technological innovation with sound governance, ethical stewardship, and long-term capacity development. By providing empirically grounded policy recommendations, this article contributes to ongoing debates on AI governance, scientific capacity building, and the modernization of laboratory systems in low-resource settings.

Abstract: Background: Saccharibacteria—historically designated candidate division TM7—and their best-characterised cultivated representative, Nanosynbacter lyticus strain TM7x challenge the classical model of a free-living, independently culturable bacterium and provide an accessible model of bacterial episymbiosis.Objective: This narrative review summarises TM7x biology and host dependence and evaluates whether current evidence supports its interpretation as a conventional periodontal pathogen or a context-dependent ecological modifier.Main findings: TM7x is an ultrasmall, genome-reduced organism whose sustained growth and replication require attachment to Schaalia odontolytica strain XH001. Detached cells remain metabolically active during horizontal transmission, using alternative energy-generating pathways until a new host is found. TM7x uses specialised type IV pili for host binding, competition and twitching motility, modifies host membrane physiology and lipid storage, and can reduce host susceptibility to bacteriophage predation. Human studies associate Saccharibacteria with periodontal and other inflammatory oral conditions, but findings are heterogeneous and do not establish causation. Experimental models indicate that some Saccharibacteria–host pairs can attenuate gingival inflammation and bone loss.Conclusion: TM7x is best viewed as a context-dependent ecological modifier rather than a conventional oral pathogen.

Abstract: Background/Objectives: Psoriasis and atopic dermatitis have historically been conceived as opposite immunological poles (Th17 versus Th2), yet molecular overlap and increasing clinical coexistence challenge this dichotomy. We aimed to adjudicate, using a multivariate approach, among three nosological architectures: a shared inflammatory–metabolic spectrum with additive coexistence (H1), distinct phenotypes with synergy (H2) and predominant overlap (H0). Methods: Cross-sectional analysis of a selected UK Biobank subsample (160,785 participants), classified by L20/L40 codes as control, isolated atopic dermatitis (n = 12,859), isolated psoriasis (n = 15,146) and coexistence (n = 1,068). Haemato-inflammatory indices, a biochemical–metabolomic panel (including GlycA) and Olink inflammatory proteins were evaluated using Cliff's delta, quantile regression with an interaction term, MANOVA/PERMANOVA, supervised classifiers, Gaussian mixture modelling, dominant-factor ordination with the Jonckheere–Terpstra test and equivalence testing (TOST; margin |δ| = 0.147). Restricted and broad control definitions were adopted. Results: Effect sizes were largely negligible (46/48 contrasts with |δ| < 0.147 under the restricted control; 38/48 formally equivalent). No psoriasis × atopic dermatitis interaction survived false-discovery-rate control (0/16), and the global multivariate interaction, although significant, was trivial (Pillai's trace = 0.0005). The dominant inflammatory factor was monotonically ordered (control < atopic dermatitis < psoriasis ≈ coexistence; Jonckheere |z| = 8.6; p < 0.001). Multivariate separation was detectable yet negligible (PERMANOVA R² = 0.6%; multiclass AUC 0.53), and latent classes did not coincide with clinical labels (adjusted Rand index = 0.004). Conclusions: The evidence favours a shared inflammatory–metabolic spectrum with approximately additive coexistence, superimposed on predominant between-group indistinguishability. Coexistence lies at the severe extreme of a common axis rather than constituting a third, emergent phenotype.

Abstract: Neonatal sepsis requires microbiological investigation, but blood culture is constrained by small sample volumes, low-density bacteremia, contamination, and delayed results. Closed-tube colorimetric loop-mediated isothermal amplification (LAMP) offers rapid, visually interpretable nucleic acid detection without conventional thermal cycling; however, performance in neonatal blood depends on the diagnostic workflow. This structured narrative review synthesizes evidence on assay design, blood preanalytics, pathogen recovery, amplification inhibition, contamination control, pathogen-specific applications, and clinical translation. Diagnostic performance is influenced by the volume collected, the fraction of the specimen entering the reaction, lysis and extraction efficiency, host-derived inhibitors, and sampling relative to antimicrobial exposure. Sealed colorimetric detection reduces post-amplification handling and amplicon dispersal, but does not prevent pre-amplification contamination or confirm target identity when nonspecific indicators are used. Most evidence derives from isolates, spiked matrices, positive blood-culture bottles, or non-neonatal specimens; prospective diagnostic-accuracy data in neonates remain scarce. Clinical translation will require validated blood-processing methods, compartmentalized target reactions, batch and sample-level controls, predefined invalid-result criteria, and panels adapted to local epidemiology. The method should therefore be evaluated as an adjunct to blood culture, which remains necessary for detecting off-panel organisms and providing phenotypic antimicrobial susceptibility results. Prospective multicenter studies should establish diagnostic accuracy, clinical utility, and safety.

Abstract: The global incidence of diseases caused by Mycobacterium abscessus (Mab), which is a nontuberculous mycobacterium (NTM), is increasing, driven by improved diagnostics and environmental changes that disrupt natural reservoirs in soil and water. These disruptions facilitate contamination of water systems. Immunocompromised individuals, particularly those with cystic fibrosis or chronic obstructive pulmonary disease, are at elevated risk, although Mab can also infect otherwise healthy individuals, causing pulmonary and cutaneous disease. Clinical management remains challenging due to intrinsic antibiotic resistance and the limited efficacy of standard anti-tuberculosis regimens. Despite this growing burden, the mechanisms governing Mab persistence and pathogenesis remain poorly defined. Progress has been constrained by the limitations of existing animal models. Mice typically clear infections rapidly, even when immunocompromised, limiting studies of chronic disease. Zebrafish support persistent infection but lack lungs and have a less developed adaptive immune system. These limitations highlight the need for alternative models. Here, we present a perspective highlighting the amphibian Xenopus laevis as a complementary model for investigating Mab chronic infection and disease. Xenopus tadpoles develop functional lungs early and possess conserved innate and adaptive immune components, including macrophages and antigen presentation pathways. Their external development allows precise control of environmental exposures and accessibility to experimentation, such as live imaging, to study Mab infection over 40 days. We discuss the application of Xenopus models to elucidate the potential role of a novel putative secondary metabolite gene cluster (SMGC) in encoding a virulence factor that promotes Mab colonization, interaction with macrophages, and persistence. Thus, X. laevis tadpoles provide a valuable experimental platform for investigating host–pathogen interactions and identifying novel therapeutic strategies.

Abstract: Typhoid fever, caused by Salmonella enterica serovars Typhi and Paratyphi, remains a major public health threat across Africa and Asia, causing substantial annual morbidity. Transmission persists in low- and middle-income countries (LMICs), where access to safe water and sanitation is limited. While improvements in water, sanitation, and hygiene (WASH) are essential, slow implementation makes vaccination the most practical preventive strategy. Current licensed vaccines have limitations, including suboptimal immune coverage in infants, limited duration of protection, and cold-chain requirements. This review examines bacteriophage-based vaccine platforms as emerging preclinical strategies for typhoid prevention. Phage technologies, including phage display, phage DNA, and hybrid models, offer potential advantages such as multivalent antigen display, projected thermostability, and cost-efficient production using bacterial manufacturing systems. Based on animal immunogenicity and proof-of-concept studies, these systems could theoretically induce durable immunity and broaden age-group protection, although their clinical feasibility and scalability remain unproven. We evaluate key technical hurdles, including endotoxin contamination, host strain engineering, and payload expression constraints. We also discuss how these potentially low-cost platforms may contribute to global antimicrobial resistance (AMR) mitigation efforts. Although phage-based vaccines remain in the preclinical stage, they represent promising research platforms for advancing vaccine equity and infectious disease resilience, provided regulatory and technical challenges are overcome. However, significant translational gaps must still be bridged before clinical application can be realized.

Abstract: Periprosthetic joint infection (PJI) remains one of the most serious complications of arthroplasty, largely due to the formation of microbial biofilms on implant surfaces. Biofilm-associated infections exhibit increased tolerance to antimicrobial therapy and host immune responses, making eradication difficult and often requiring repeated surgical interventions. Consequently, there is a growing need for effective local therapeutic strategies capable of delivering high concentrations of antimicrobial agents directly to the site of infection while minimizing systemic toxicity. Hydrogels have emerged as promising drug delivery platforms for the management of biofilm-associated PJI. Their biocompatibility, injectability, high water content, and tunable physicochemical properties enable controlled and localized release of therapeutic agents within the infected peri-implant environment. This narrative review summarizes recent advances in hydrogel-based approaches, including antibiotic-loaded hydrogels, systems incorporating anti-biofilm enzymes, bacteriophage-loaded formulations, and nanoparticle-enhanced platforms. It also highlights future research directions, with particular emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydro-gel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI. Particular attention is given to stimuli-responsive (“smart”) hydrogels that release therapeutic payloads in response to infection-related triggers such as pH changes, with emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI.

Abstract: Metacaspases are cysteine proteases, found in plants, fungi, and protists. They are structural orthologs of caspases, which orchestrate apoptosis in metazoa. However, metacaspases differ from caspases in that they cleave after arginine or lysine instead of aspartate, most are activated by calcium, and they do not target the same range of proteins as caspases. The Candida albicans metacaspase, Mca1p mediates cell death in response to various stresses but also possesses pro-life functions such as proteostasis. This research report highlights differences in the effect of MCA1 deletion on cell death and virulence, depending on whether cells originate from exponential or stationary phase culture.

Abstract: Respiratory viral infections are a major cause of global morbidity and mortality, partly because they increase susceptibility to secondary bacterial pneumonia and sepsis. Coronaviruses, influenza viruses, parainfluenza viruses, rhinoviruses, and respiratory syncytial virus have each been associated with impaired macrophage antibacterial function, although the underlying evidence differs among virus families. Direct lysosomal-pH measurements and mechanistically resolved links between infection and lysosomal de-acidification are strongest for coronaviruses. Using β-coronaviruses as the primary model for the effect of direct lysosomal disruption on macrophage antimicrobial capacity, this review examines lysosomal exploitation during viral egress, impaired phagosome-lysosome fusion, E-protein-mediated proton conductance, and ORF3a-associated lysosomal injury. It further proposes that the magnitude of these effects is shaped by host-dependent immunometabolic processes. Mitochondrial dysfunction, NAD⁺ depletion, and disrupted mitochondria-lysosome coupling may reduce the ability of macrophages to preserve lysosomal acidity, autophagic competence, and bacterial killing during viral challenge. Together, these mechanisms describe how coronavirus infection compromises macrophage antibacterial defense, and how the resulting susceptibility to secondary bacterial infection is further modulated by the metabolic and inflammatory state of the host cell.

Abstract:

Background: Ankylosing spondylitis (AS) associated with Crohn’s disease (CD) is a nosological form of spondyloarthropathies with a low population prevalence. The pathogenesis of this disease is not fully understood, and there are no precise differential diagnostic methods to distinguish AS associated with CD from AS and CD separately in the early stages of the disease. The main objective for this study is to define lymphocyte-mediated immunity in patients with AS associated with CD. Methods: For the pilot study, we recruited 4 groups: CD (n=16), AS+CD (n=13), AS (n=13) and healthy controls (HC, n=26). Immune phenotyping of peripheral blood lymphocytes via flow cytometry. Results: In the AS+CD group, circulating regulatory T cells (Treg) levels were increased compared to the other groups. The frequency of CD73+ Tregs within the effector memory (EM) compartment was also elevated in the AS+CD group relative to the AS and CD groups alone. At the same time, the EM Tcyt and EM Th populations were lower in the AS+CD group compared to the CD group. Tfh17 levels were lower in the AS+CD group than in the AS group and showed a positive correlation with Bm5 and switched memory B cells. Additionally, Tfh17 and switched memory B cells correlated negatively with acute-phase markers, whereas Tfh2 correlated positively with the BASDAI activity index. Conclusions: In patients with AS associated with CD, exhaustion of the regulatory compartment of adaptive immunity is seen, whereas the humoral component appears oriented towards resolving the inflammatory responses.

Abstract: Host immunological pathways can be categorized into IgM dominant innate immunological pathways, IgG dominant eradicable adaptive immunological pathways, and IgA dominant tolerable adaptive immunological pathways. The tolerable adaptive immune responses can be TH9, TH17, TH3, and TH4. Here, I further discuss the key cytokine in the TH4 immune response is interleukin-2. Once we know the whole framework of host immunological pathways, we can develop better prevention and control strategies combating infectious diseases and autoimmune disorders.

Abstract: One of the main causes of drug resistance in malignancies is metabolic reprogramming in the tumor microenvironment (TME). To maintain growth and alter the TME, cancer cells frequently rewire their metabolism, resulting in circumstances including food deprivation, hypoxia and acidity that hinder antitumor immune responses. The TME’s immune cells also experience metabolic changes, often taking on immunosuppressive characteristics that accelerate tumor growth and dampen the effectiveness of treatment. B cells are integral to the adaptive immune response, primarily through MHC class II-mediated antigen presentation and immunoglobulin secretion. Emerging evidence indicates that the functional role of tumor-infiltrating B cells is highly heterogeneous across malignancies. While their antigen-presenting capacity is generally associated with anti-tumor immunity, the contribution of B cell-derived antibodies remains ambiguous and context-dependent. Additionally, regulatory B cell subsets (Bregs) exert immunosuppressive effect within the TME by secreting anti-inflammatory cytokines such as interleukin (IL)-10 and tumor growth factor (TGF)-β, thereby facilitating immune evasion. Herein, we summarise the current understanding of B-cell functions in tumor immunology, which may shed light on potential therapeutic strategies against cancer.

Abstract: Aspergillus species are saprophytes, found in soil, decaying matter and on the surface of plants. Some species are pathogens of humans, other animals or plants or cause food spoilage. Invasive aspergillosis affects three million people, mostly immunocompromised individuals, and mortality is around 50% where treatment is provided and almost 100% without treatment. Allergic bronchopulmonary aspergillosis affects five million people, particularly asthmatics and cystic fibrosis patients. Resistance to azole antifungals is rising, possible because of agricultural use of azoles. This review discusses Aspergillus species, aspergillosis and allergic conditions caused by Aspergillus, immune reactions and ways in which Aspergilli counteract immune responses, the rise of antifungal resistance and the dispersal of Aspergillus spores and mycelial fragments and suggests future prospects, including possible research directions and methods of detection and treatment.

Abstract: The intensification of human–companion animal interactions has amplified the risk of zoonotic infections and antimicrobial resistance at the human–animal–environment interface. Dogs and cats serve as important reservoirs for a range of fungal pathogens, including dermatophytes such as Microsporum canis, yeast-associated infections involving Malassezia species, and environmentally acquired systemic mycoses. Transmission to humans occurs through direct contact with infected animals, indirect exposure via contaminated fomites, and shared environmental sources. Urbanisation, increasing pet density, climate change, and environmental disturbance have further reshaped the epidemiology of fungal zoonoses, facilitating outbreaks and enhancing fungal adaptation to warm-blooded hosts. In parallel, inappropriate antimicrobial and antifungal use in companion animals has contributed to the emergence of resistant pathogens, including mobile colistin resistance (mcr) genes and antifungal-resistant dermatophytes, raising serious public health concerns. Viral infections, such as SARS-CoV-2, may exacerbate this risk by impairing host immunity and predisposing animals and humans to secondary fungal infections. This review critically examines pet-associated fungal infections, their transmission dynamics, and the role of close contact, urbanisation, and antimicrobial misuse in driving zoonotic risk, highlighting the urgent need for integrated One Health surveillance, responsible pet ownership, and evidence-based policy interventions.

Abstract: The use of the word inflammation in recent literature appears to have superseded the classical definition of the word. However, a precise new definition has not yet emerged. As a result, the boundaries of the concept are hazy and it needs to be examined critically whether everything in the semantic basket is indeed “inflammation”. Similar to almost all genes, molecules and pathways, inflammation associated cells and molecules also have a number of normal physiological functions unrelated to defence. Therefore, altered expression of these may not always reflect inflammation. If all the range of functions are also to be called inflammation, in the entire life ranging from embryo implantation to death, the body can be said to be always in a state of inflammation. This takes aways the need for the concept itself. As a result of the ambiguous definition, a number of anomalies are associated with the concept of inflammation. In particular the concept of chronic systemic inflammation is laid with multiple anomalies which might be misleading our understanding of health and disease. On the foundation of evolutionary logic, a new and clearer perspective of inflammation can emerge. We discuss the foundations of the new perspective and its relevance to health, disease and medicine.

Abstract: Shovill is a Unix command-line bioinformatics pipeline for performing de novo genome assembly of haploid microbial genomes from accurate paired-end short-read sequences, most commonly generated on the Illumina™ platform. Shovill is a full end-to-end workflow which accepts reads in FASTQ format and generates assembled contigs in FASTA format. It trims reads, sub-samples reads to an appropriate depth, corrects reads, stitches overlapping read pairs together,, de novo assembles the reads into contigs, and self-corrects any assembly errors. Each step is optimised to reduce RAM usage and maximise CPU usage. Shovill is written in Perl 5 and is available from github.com/tseemann/shovill under an open-source GPL 2.0 licence.

Abstract: Antimicrobial resistance (AMR) is a growing worldwide challenge, treatment options for bacterial infections are increasingly limited. Non-typhoidal Salmonella (NTS), particularly Salmonella enterica serovar Typhimurium, poses a serious threat to public health due to rising antimicrobial resistance. It can cause invasive bloodstream infections that have a high death rate. This study aimed to identify and isolate exclusively lytic bacteriophages that target multidrug-resistant Salmonella Typhimurium (ATCC 13311) from river water and poultry farm environments in Addis Ababa, Ethiopia and assessed their potential as an alternative treatment. A total of 38 environmental samples were collected from poultry farms and rivers. From these samples, 22 different bacteriophages were successfully isolated using S. Typhimurium ATCC 13311 as the host strain. The majority (63.6%) were isolated from river water samples. Spot assays were used to isolate phages, and the double-layer agar method (DLA) was used for purification. Characterization of phages of phages performed by PCR-based identification and classification, latent period determination, plating efficiency, burst size, stability testing, and assessment of in vitro bactericidal activity. Host range analysis showed that all isolates were active against the primary host, and four isolates showed cross-genus efficacy against specific pathotypes of Escherichia coli. The latent periods of the isolated phages ranged from 10 to 20 minutes, indicating a wide range of infection kinetics. Some of the most productive isolates attained Peak titers as high as 10¹³ PFU/mL, indicating significant replication capacity. Additionally, the ideal multiplicity of infection differed significantly amongst isolates, ranging from 0.001 to 100. Regarding environmental stability, all phages were active in a pH range of 5 to 9 and withstood temperatures ranging from 4°C to 37°C. Molecular analysis classified most isolates into the T4-like and T7-like lineages, two distinct phage groups with known lytic characteristics. This study demonstrates that locally isolated lytic bacteriophages can effectively inhibit multidrug-resistant Salmonella Typhimurium ATCC 13311. The findings support their potential as safe and effective biocontrol agents for combating MDR S. Typhimurium infection. However, clinical trials, in vivo research, and genome sequencing are necessary to confirm these phages' effectiveness and safety.

Abstract: Desmogleins (Dsg) are transmembrane proteins involved in cell-cell junctions. Keratinized epithelia, such as skin, express several forms of Dsg. Dsg4 deficiency is associated with hair loss in humans, mice, and rats. Recently, we reported that topical administration of imiquimod (IMQ) to Dsg4-deficient rats exacerbates skin inflammation. Different immune-mediated diseases, including Psoriasis, Spondyloarthritis, Systemic Lupus Erythematosus, and Atopic Dermatitis, involve skin inflammation. Unfortunately, the role of Dsg4 in the induction of humoral immunity has not been addressed. Our work aimed to determine whether Dsg4 deficiency impairs the induction of an antigen-specific immune response. For this purpose, Dsg4 deficient Oncins France Colony A hairless/hairless (OFA) and wild-type Sprague-Dawley (SD) rats were treated with IMQ, or vaseline, to evaluate lymph node (LN) expansion. We found that OFA rats exhibited higher LN size with histological differences compared to SD rats. Brachial LN expansion after topical IMQ treatment was reduced in OFA rats compared to SD. Surprisingly, when we evaluated the induction of the immune response to intradermal ovoalbumin (OVA) challenge, we observed that OFA rats showed lower levels of OVA-specific IgM, IgG, IgG2a and IgA than the SD group. Although further investigations are necessary, our results suggest a novel role for Dsg4 in supporting humoral immunity under inflammatory conditions.