Toxoplasmosis is a zoonotic disease caused by the apicomplexa protozoan parasite Toxoplasma gondii. This disease is a health burden, mainly in pregnant women and immunocompromised individuals. Dehydroepiandrosterone (DHEA) has proved to be an important molecule that could drive resistance against a variety of infections, including intracellular parasites such as Plasmodium falciparum and Trypanozoma cruzi, among others. However, to date it has not been explored the role of DHEA on T. gondii. In here, we demonstrated for the first time the toxoplasmicidal effect of DHEA on extracellular tachyzoites. Ultrastructural analysis of treated parasites showed that DHEA alters the cytoskeleton structures, leading to the loss of the organelle structure and organization, as well as the loss of the cellular shape. In vitro treatment with DHEA reduces the viability of extracellular tachyzoites and passive invasion process. 2D SDS-PAGE analysis revealed that in the presence of the hormone a progesterone receptor membrane component (PGRMC) with a cytochrome b5 family heme/steroid binding domain-containing protein was expressed, while the expression of proteins that are essential for motility and virulence was highly reduced. Finally, in vivo DHEA treatment induced a reduction of parasitic load in male, but not in female mice.

Toxocara canis is a helminth parasite with importance in public and veterinary health. Although different studies have evaluated the immune response, to date there are no studies where it is analyzed from the point of view of sexual dimorphism. At 7 days of infection, female rats had a higher number of larvae in the liver, while male rats had them in the lungs. The percentages of immune cells were evaluated, and in most cases, no significant differences were observed. Regarding the cytokines production, infection can generate a decrease in Th1 such as IL-1β in both sexes and IL-6 only in females. In the case of Th2, IL-4 increases only in infected males and IL-5 increases in males and decreases in females due to the effect of infection. IL-10 also decreases in both sexes as a consequence of the infection and TGF-β only in females. Finally, the infection generates the production of antibody against the parasite, however, their quantity is lower in females. Thus, this study demonstrates that Toxocara canis infection is dimorphic and affects females more than males. This is due to a polarization of the inadequate immune response, which is reflected as a higher parasite load in this sex.

Mast cells (MCs) play a crucial role during infections with Leishmania, that is transmitted through the bite of an infected sand fly that injects saliva together with the parasite. Sand fly saliva is a complex fluid that modulates the host immune response. In addition, hormonal factors modulate the host immune response, impacting the susceptibility to infections. Thus, to assess the impact of androgens and salivary proteins of sand fly vectors on the mast cell (MC) response to Leishmania infections, we infected orchiectomized male mice with the parasite in the presence or absence of sand fly salivary proteins and analyzed the inflammatory response of MCs. Our results showed a differential MC response to the parasite and to vector salivary proteins in mice deprived of gonadal hormones, as compared to sham-operated mice. Orchidectomy induced a different pattern of activation in MC of animals infected with Leishmania and vector-salivary proteins. Our results show that during Leishmania infection, androgens modulate the innate immunity response against the parasite and salivary proteins of the sand fly vector.

Background: Metastasis is a complex process that involves the spread of the tumor to distant parts of the body from its original site. Metastatic dissemination represents the main physiopathology of cancer. Soluble factors such as cytokines have been closely related to breast cancer (BC) metastasis. Bisphenol A (BPA) is an endocrine disrupting chemical compound with estrogenic properties, which exposure in the early stages of neonatal life leads to an increase in the size and weight of breast tumors and cellular changes in the tumoral immune microenvironment. Methods: Thus, we used female BALB/c mice that were exposed neonatally to a single dose of BPA. Once sexual maturity was reached, a mammary tumor was induced injecting 4T1 cells in situ. After 25 days of injection, we evaluated endocrine alterations, cytokine expression, tissue alterations denoted by macro and micro metastases in the lung, and metastasis-induced cell infiltration. Results: BPA neonatal treatment did not show significant endocrine alterations. Nevertheless, BPA induced a great rate of metastasis to the lung associated with higher intratumoral expression of IL-1b, IL-6, IFN-g, TNF-a and VEGF. Conclusions Our data suggest that cytokines are key players in BC metastasis induction, and that BPA is a risk factor to be considered. This knowledge must be considered with the aim of recognizing environmental pollution in the clinical history of patients to possibly counter BC metastases.

Parkinson’s disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin or tween-80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four h and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin reduced significantly the MPP+-induced damage compared to MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson’s disease, and since there is not currently a proteomic map of the Nigro striatum of rats, and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation are decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and for the first time the molecular mechanisms involved in this protective effect.

Public concern has emerged about the effects of endocrine disruptor compounds (EDCs) on neuropsychiatric disorders. Preclinical evidence suggests that exposure to EDCs is associated with the development of the major depressive disorder (MDD) and could result in neural degeneration. The interaction of EDCs with hormonal receptors is the best-described mechanism of their biological activity. However, the dysregulation of the hypothalamic-pituitary-gonadal adrenal axis has been reported and linked to neurological disorders. On the other hand, at a worldwide level and in Mexico, the incidence of MDD has recently been increasing. Of note, in Mexico, there are no clinical associations on blood levels of EDCs and the incidence of the MDD. Methodology: Thus, we quantified for the first time the serum levels of parent compounds of two bisphenols and four phthalates in patients with MDD. Results: The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP), and di-ethyl-phthalate (DEP), bisphenol A (BPA), and bisphenol S (BPS) were determined with a gas chromatograph-mass spectrometer. Results/ conclusion: We found significant differences between concentrations of BBP between controls and patients with MDD.

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 explored the hypothesis that progesterone direct effect on Trichinella spiralis might be mediated indeed by a new steroid-binding parasite protein. Our first results showed that Progesterone decreases the parasite molting rate. We amplify, isolated, cloned and sequenced the PGRMC2 sequence using specific primers from known species. Furthermore, we expressed the protein and developed an antibody to performance immunofluorescent confocal microscopy, where detected that parasite cells showed expression of a P4-binding protein exclusively located at the oocyte and the parasite´s cuticle. Presence of the PGRMC2 protein in these cells was also confirmed by western blot and flow cytometry. Molecular modeling studies accompanied by computer docking using the sequenced protein showed that PGRMC2 is potentially able to bind steroid hormones such as progesterone, estradiol, testosterone, and dihydrodrotestosterone with different affinities. Phylogenetic analysis and sequence alignment clearly demonstrated that Trichinella spiralis PGRMC2 is related to a steroid-binding protein of another platyhelminths. Progesterone may probably act upon Trichinella spiralis oocytes probably by binding to PGRMC2. This research has implications in the field of host-parasite co-evolution as well as the sex-associated susceptibility to this infection. In a more practical matter, present results may contribute to the molecular design of new drugs with anti-parasite actions.