Littérature scientifique sur le sujet « Sex-related Immunity »

Abstract Glioblastomas (GBMs) are aggressive, inevitably lethal brain tumors that are massively infiltrated by myeloid cells supporting tumor growth. The main myeloid cell populations encompass brain-resident microglia, bone marrow (BM)-derived monocytes/macrophages and dendritic cells. Interestingly, patients with glioblastoma show sex-dependent differences in the incidence rate (male-to-female ratio of 1.6:1 in GBMs and 2:1 in most malignant mesenchymal GBMs), transcriptomic profiles and patient responses to a standard therapy. Sex-related differences such as higher expression of pro-inflammatory genes in female microglia and stronger upregulation of MHCII coding genes in microglia from male GL261-bearing mice were detected (Ochocka et al. 2021). We employed Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) to reliably dissect myeloid cell identities, states and evaluate dynamics of myeloid infiltration during progression of murine GL261 gliomas. We demonstrate the diversity of myeloid cells within the glioma microenvironment: glioma-activated microglia are the major source of cytokines attracting other immune cells, whereas BM-derived cells show the monocyte-to-macrophage transition and immunosuppressive phenotypes. This transition is coupled with a phenotypic switch from the IFN-related to antigen-presentation and tumor-supportive signatures. Moreover, we found striking sex-dependent differences in transcriptional programs and composition of myeloid cells in gliomas. Higher abundance of protumor macrophages in males correlated with greater tumor size. Re-analysis of single-cell omics data from human GBMs revealed the predominance of inflammatory monocytes in female GBMs and abundance of protumor macrophages in male GBMs. Our findings expand understanding of the complexity of anti-tumor immune responses in gliomas and may guide future therapies in consideration of patient sex. Studies supported by National Science Centre Poland research grants PRELUDIUM16 2018/31/N/NZ3/01696, OPUS 14 2017/27/B/NZ3/01605 and 2020/39/B/NZ4/02683.

Abstract Aging is accompanied by striking changes in chromatin and gene expression across cell types and species. Yet, how chromatin landscapes change with age and regulate transcription, and how epigenomic changes in turn influence aging in response to external or internal cues, is largely unknown. In addition, accumulating evidence indicates that sex hormones play a key role in driving aspects of cellular and molecular sex-dimorphism. In parallel to sex hormones, karyotypic sex (i.e. XX vs. XY) is also likely to have important impact outside of gonadal sex determination. A key compartment whose activity can be actively modulated by sex-dimorphic mechanisms throughout life is the immune system, whose function declines sharply with aging and may be actively modulated by sex. Indeed, aspects of the immune responses differ between sexes, with a more robust immune response in females and an increased susceptibility to infection in males. Thus, our main cell models of study are key components of the innate immune system and the inflammatory response: macrophages, which accomplish key tasks such as phagocytosis, antigen presentation and cytokine production, and neutrophils, the most abundant leukocyte type serving as a “first line of defense” against infection. Excitingly, we and others have observed strong sex-related differences in the transcriptional and functional phenotypes of these cells and have observed sex-dimorphic “omic” trajectories for these cells with aging. Based on our data and published literature, it is likely that mechanisms involving both gonadal hormones and sex chromosomes may fine-tune different aspects of immunity and, thus, overall health and lifespan.

Evidence for age-related changes in innate and adaptive immune responses is increasing in wild populations. Such changes have been linked to fitness, and knowledge of the factors driving immune response variation is important for understanding the evolution of immunity. Age-related changes in immune profiles may be owing to factors such as immune system development, sex-specific behaviour and responses to environmental conditions. Social environments may also contribute to variation in immunological responses, for example, through transmission of pathogens and stress arising from resource and mate competition. Yet, the impact of the social environment on age-related changes in immune cell profiles is currently understudied in the wild. Here, we tested the relationship between leukocyte cell composition (proportion of neutrophils and lymphocytes [innate and adaptive immunity, respectively] that were lymphocytes) and age, sex and group size in a wild population of European badgers ( Meles meles ). We found that the proportion of lymphocytes in early life was greater in males in smaller groups compared to larger groups, but with a faster age-related decline in smaller groups. By contrast, the proportion of lymphocytes in females was not significantly related to age or group size. Our results provide evidence of sex-specific age-related changes in immune cell profiles in a wild mammal, which are influenced by the social environment.

The current knowledge of sex-dependent differences in adipose tissue biology remains in its infancy and is motivated in part by the desire to understand why menopause is linked to an increased risk of metabolic disease. However, the development and characterization of targeted genetically-modified rodent models are shedding new light on the physiological actions of sex hormones in healthy reproductive metabolism. In this review we consider the need for differentially regulating metabolic flexibility, energy balance, and immunity in a sex-dependent manner. We discuss the recent advances in our understanding of physiological roles of systemic estrogen in regulating sex-dependent adipose tissue distribution, form and function; and in sex-dependent healthy immune function. We also review the decline in protective properties of estrogen signaling in pathophysiological settings such as obesity-related metaflammation and metabolic disease. It is clear that the many physiological actions of estrogen on energy balance, immunity, and immunometabolism together with its dynamic regulation in females make it an excellent candidate for regulating metabolic flexibility in the context of reproductive metabolism.

Immune defences often trade off with other life-history components. Within species, optimal allocation to immunity may differ between the sexes or between alternative life-history strategies. White-throated sparrows ( Zonotrichia albicollis ) are unusual in having two discrete plumage morphs, white-striped and tan-striped. Within each sex, white-striped individuals are more aggressive and provide less parental care than tan-striped individuals. We extended immunocompetence handicap models, which predict sex differences in immunity and parasitism, to hypothesize that infection susceptibility should be greater in white-striped than tan-striped birds. We inoculated birds of both morphs with malarial parasites. Contrary to our prediction, among birds that became infected, parasite loads were higher in tan-striped than white-striped individuals and did not differ between the sexes. Circulating androgen levels did not differ between morphs but were higher in males than females. Our findings are not consistent with androgen-mediated immunosuppression. Instead, morph differences in immunity could reflect social interactions or life-history-related differences in risk of injury, and/or genetic factors. Although plumage and behavioural morphs of white-throated sparrow may differ in disease resistance, these differences do not parallel sex differences that have been reported in animals, and do not appear to be mediated by differences in androgen levels.

Background. The incidence of oral mucosa cancer (OMC) is higher in people over 50 years of age, and the aggressiveness of the course of the disease is higher in people under 50 years of age. In this context, it is of interest to clarify the mechanisms of immune disorders characteristic of patients of different age groups.Aim. To research systemic and local immunity in OMC patients and the relationship of peripheral blood lymphocyte population (PBLs) and tumor infiltrating lymphocytes (TILs) with the patient’s sex and age.Materials and methods. PBLs and TILs effector and suppressor populations were studied by flow cytometry in OMC patients aged 29 to 84 years.Results. The percentage of CD3-, CD3+CD4+ and CD3+CD8+T cells, regulatory CD4+CD25+CD127low/ –(CD4Treg) and CD8+CD11b–CD28–(CD8Тreg) T lymphocytes, CD4+PD-1+ and CD8+PD-1+ T cells was increased in TILs compared to PBLs. The levels of cytotoxic CD8+CD11b+CD28– T lymphocytes, NK, CD8+Perforin+ and CD16+Perforin+ cells in TILs were lower than in PBLs. The relationship between the level of CD4Treg and other TILs and PBLs depended on the patient’s sex. Age-related changes in the levels of NK and CD8 T-cells were observed in men, and CD4Treg – in women.Conclusion. Local immunity in OMC patients is highly immunosuppressive. The sex of patients influences the relationship between CD4Treg and other populations of PBLs and TILs, as well as age-related changes in the OMC patients’ immune system. This investigation results can make a certain contribution to personalized treatment of patients with OMC, taking into account differences in systemic and local immunity and in the immune response to the tumor in patients of different sex and age.

Abstract Ease of access to circulating peripheral blood cells (PBMCs) can offer unique insights into human immune function, as well as responses to vaccination and infection. Nevertheless, PBMC heterogeneity has been under-appreciated since results obtained from mixed populations may reflect changes in subset abundance as opposed to true age-related changes involving a specific subset. Technological advances have allowed for the examination of age-related heterogeneity with regards to systemic cytokine levels, immune cell frequencies and chemokine receptor expression by peripheral lymphocytes. Furthermore, introduction of sex as a variable in the examination of human PBMCs adds additional dimorphism to the study of aging and immunity including differences in epigenetic modifications, levels of pro-inflammatory activity and adaptive immunity.

Mammalian sex chromosomes evolved from an ordinary pair of autosomes. The X chromosome is highly conserved, whereas the Y chromosome varies among species in size, structure, and gene content. Unlike autosomes that contain randomly mixed collections of genes, the sex chromosomes are enriched in testis-biased genes related to sexual development and reproduction, particularly in spermatogenesis and male fertility. This review focuses on how sex chromosome dosage compensation takes place and why meiotic sex chromosome inactivation occurs during spermatogenesis. Furthermore, the review also emphasizes how testis-biased genes are enriched on the sex chromosomes and their functions in male fertility. It is concluded that sex chromosomes are critical to sexual development and male fertility; however, our understanding of how sex chromosome genes direct sexual development and fertility has been hampered by the structural complexities of the sex chromosomes and by the multicopy nature of the testis gene families that also play a role in immunity, cancer development, and brain function.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. Nowadays, COPD is the fourth leading cause of death in the world and its morbidity and mortality are constantly increasing. COPD is characterized by emphysema and chronic bronchitis, usually present simultaneously, with a wide range of severity. COPD was considered as a lung-restricted disease for many years, but from 2000 increasing new evidence, including a number of comorbid conditions accompanying this pathology and the presence of systemic inflammation, indicate that COPD should be considered a systemic disease. Systemic inflammation is the most common systemic manifestation of COPD, and it is associated with a progressive worsening of symptoms and comorbidities. In addition to soluble inflammatory markers, such as TNFα, several research groups focused their attention on peripheral blood leukocytes to assess the changes occurring in these cells in COPD and their relation to the inflammatory pattern in the lungs. However, the data about peripheral leukocyte composition and functional changes in COPD are quite controversial. COPD was traditionally considered as a disease affecting principally males, but rising evidence show that it probably equally concerns male and female populations. However, there are differences in symptoms severity, disease progression and treatment benefits between male and female COPD. Yet, despite the clear evidence of sexual dimorphism in COPD manifestation and progression, there are, to our knowledge, no publications about the difference in the immune state between male and female COPD. Given the lack of data assessing gender-related differences in COPD systemic immune system manifestations and the discordance in the data about circulating leukocyte alterations in COPD, we aimed at thoroughly characterize circulating leukocyte alterations in COPD as compared to age-matched controls. Additionally, results have been stratified according to gender in order to identify male- and/or female-specific COPD immunophenotype. Blood samples from 50 COPD patients and 63 age and sex-matched controls have been collected and analyzed. Flow cytometry analysis revealed the existence of well-defined gender-related pattern of circulating leukocytes in COPD. Specifically, while neutrophilia and increased neutrophil to lymphocyte ratio are hallmarks of COPD in male, on the contrary, female COPD are characterized by a generalized leukopenia. Remarkably, we demonstrated that T cell exhaustion is more prominent in female COPD, nevertheless it increases with disease severity in both male and female groups. Moreover, several observations suggest that that T cells decrease in both male and female COPD may be related to PD1-dependent apoptosis. Additionally, we showed that absolute numbers and/or frequencies of several leukocyte populations correlate with different clinical parameters of COPD disease severity. Given the relevance of the increase in neutrophil absolute count and frequency in male COPD, we subsequently characterized circulating neutrophil phenotype, function and transcriptome of male COPD and related controls. Despite the fact that phenotype and function of neutrophils purified from COPD subjects were comparable to those from controls, differential gene expression analysis highlighted a number of differentially expressed genes. On the basis of the correlation of the differentially expressed genes with the disease severity, we identified a neutrophil-specific COPD signature. Finally, this proposed COPD signature was successfully validated on a larger cohort of male COPD subjects.

 Evidence suggests that the majority of adults develop detectable levels of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies following infection with SARS-CoV-2 (moderate strength of evidence* [SoE]).  IgM levels peak approximately 20 days after symptom onset or RT-PCR diagnosis and subsequently decline. IgG levels peak approximately 25 days after symptom onset or RT-PCR diagnosis and may remain detectable for at least 120 days (moderate SoE*).  Almost all adults develop neutralizing antibodies in response to SARS-CoV-2 infection, and these antibodies may remain detectable for at least 152 days (low SoE*).  A small percentage of people do not develop antibodies in response to SARS-CoV-2 infection for reasons that are largely unclear but may be related to less severe disease or absence of symptoms.  Antibody prevalence does not appear to vary by age or sex, but older age may be associated with higher antibody levels (low SoE*). Non-White race may be associated with higher antibody prevalence and levels (low SoE*). COVID-19 severity and presence of symptoms may also be associated with higher antibody prevalence or levels (low SoE*). More evidence is needed to draw stronger conclusions regarding how the antibody response varies by patient characteristics and disease factors.  Studies to date have not established the relationship between the development of antibodies after RT-PCR-diagnosed SARS-CoV-2 infection and the risk of reinfection. Studies based on index serologic testing suggest that the presence of antibodies is associated with a lower risk of a subsequent positive SARS-CoV-2 RT-PCR test.