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Review
. 2021 Aug 31:12:720952.
doi: 10.3389/fimmu.2021.720952. eCollection 2021.

Sex Differences in Immunity to Viral Infections

Henning Jacobsen  1 , Sabra L Klein  1
Affiliations
Review

Sex Differences in Immunity to Viral Infections

Henning Jacobsen et al. Front Immunol. .

Abstract

The ongoing COVID-19 pandemic has increased awareness about sex-specific differences in immunity and outcomes following SARS-CoV-2 infection. Strong evidence of a male bias in COVID-19 disease severity is hypothesized to be mediated by sex differential immune responses against SARS-CoV-2. This hypothesis is based on data from other viral infections, including influenza viruses, HIV, hepatitis viruses, and others that have demonstrated sex-specific immunity to viral infections. Although males are more susceptible to most viral infections, females possess immunological features that render them more vulnerable to distinct immune-related disease outcomes. Both sex chromosome complement and related genes as well as sex steroids play important roles in mediating the development of sex differences in immunity to viral infections.

Keywords: SARS-CoV-2; T cells; antibodies; inflammation; influenza; innate immunity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mechanistic causes of sex differences in immunity to viral infection. Biological sex is defined by sex chromosome complement (i.e., XX or XY) in a majority of individuals, which results in sex differential development of gonadal tissues in utero, with development of ovaries in XX individuals and testes in XY individuals. The development of testes in XY individuals is primarily mediated by the expression of SRY on the Y chromosome, which encodes for testes determining factor. The ovaries and testes secrete differential concentrations of sex steroids, including estrogens, progesterone, and androgens. Numerous immune cells, including but not limited to macrophages, dendritic cells, neutrophils, NK cells, T cells, and B cells express cytoplasmic receptors for sex steroids, which can transcriptionally regulate gene expression, signal transduction, and responses of immune cells following viral infection. As a result, biological females tend to have greater immune system activation resulting in faster clearance of viruses, but also increased probability of developing immune-mediated pathology. In biological males, reduced immune system activation results in slower clearance of viruses, and in some cases viral persistence as well as reduced vaccine-induced immunity. Created using Biorender.
See this image and copyright information in PMC

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