Trends in Immunology
ReviewSeXX matters in immunity
Section snippets
Sex: a major determinant of an immune response
Accumulating evidence supports a role for sex-based differences in susceptibility to and severity of infectious diseases, in response to vaccination and medications, and in both the incidence and pathogenesis of autoimmune diseases 1, 2. Sex bias in the immune response could result from direct effects of an individual's sex chromosome complement, for example, X- or Y-linked genes, from indirect effects of the sex chromosomes, for example, sex hormones, or from environmental risk factors that
Sex bias in infectious diseases
It has long been known that, in general, males are more susceptible to infectious diseases than females. Multiple studies have documented this sex bias in susceptibility to certain bacterial, parasitic, and viral infections (Box 1); both in humans and in a variety of other species (reviewed in [4]). Although epidemiological data on human sex bias in infectious diseases incite interesting questions, biological effects may be obscured by variables such as sex-specific behaviors that may modify
Mechanisms determining sex-specific immunity
Sex hormones exert potent effects on immune cell subsets. The global gene expression profile of peripheral blood mononuclear cells (PBMCs) from young and elderly men and women has revealed age- and sex-dependent alterations in immune cell transcriptomics [26]. The ways in which sex-dependent immune cell phenotypes are influenced by sex hormones is an emerging field, and accumulating data are providing new insights. Sex steroid hormones exert their functions by binding to nuclear receptors that
Environmental, epigenetic, and pregnancy-related modification of sex-specific immunity
There is emerging evidence that epigenetic and environmental (particularly, microbiome-related) factors influence the expression of sex-specific immune phenotypes. In addition, dramatic changes in sex hormone levels during pregnancy may simultaneously promote tolerance to the fetus, while creating vulnerability to pathogens. Some recent progress in these fields is discussed below.
Concluding remarks
Recent advances in our understanding of how sex influences the immune response include evidence that the microbiome and epigenetic phenomena, including expression levels of miRs, contribute significantly to defining an immune response. Moreover, recent data further specify the direct effects of sex hormones on individual immune cell subsets. Age-dependent changes in the transcriptome, hormone levels, and immune cell responsiveness, all contribute to the sex differential in susceptibility to and
Acknowledgments
ENF is a Tier 1 Canada Research Chair. JGM is supported by a Postdoctoral Fellowship from the Canadian Institutes of Health Research.
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