Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection - PubMed (original) (raw)

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Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

Sapana Kadel et al. Front Immunol. 2018.

Abstract

Sex differences in the incidence and severity of respiratory virus infection are widely documented in humans and murine models and correlate with sex biases in numbers and/or functional responses of innate immune cells in homeostasis and lung infection. Similarly, changes in sex hormone levels upon puberty, pregnancy, and menopause/aging are associated with qualitative and quantitative differences in innate immunity. Immune cells express receptors for estrogens (ERα and ERβ), androgens (AR), and progesterone (PR), and experimental manipulation of sex hormone levels or receptors has revealed that sex hormone receptor activity often underlies sex differences in immune cell numbers and/or functional responses in the respiratory tract. While elegant studies have defined mechanistic roles for sex hormones and receptors in innate immune cells, much remains to be learned about the cellular and molecular mechanisms of action of ER, PR, and AR in myeloid cells and innate lymphocytes to promote the initiation and resolution of antiviral immunity in the lung. Here, we review the literature on sex differences and sex hormone regulation in innate immune cells in the lung in homeostasis and upon respiratory virus infection.

Keywords: androgen; estrogen; innate immunity; lung; respiratory virus; sex hormones.

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Figures

Figure 1

Figure 1

Sex differences in innate immune responses during the effector and repair phases of respiratory virus infection. Here, we summarize reports of sex differences or sex hormone receptor regulation of innate immune cells. The pink shaded area indicates cells and pathways reported to be elevated in females and/or upon estrogen/ER activity. The blue shaded area indicates cells and pathways reported to be increased in males and/or upon androgen/AR activity. A balanced type 1 immune response involving different innate immune cells is required early post-infection in the lung for viral clearance. At later stages of infection, regulatory immune responses mediated by alveolar macrophages and innate lymphoid cells are important for the repair of damaged tissues and renewal of barrier integrity. Sex differences in numbers, functional responses, plasticity, and survival of innate immune cells regulate the proinflammatory/effector and regulatory/repair phases of infection.

References

    1. Mizgerd JP. Lung infection – a public health priority. PLoS Med (2006) 3(2):e76. 10.1371/journal.pmed.0030076 - DOI - PMC - PubMed
    1. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol (2016) 16(10):626–38. 10.1038/nri.2016.90 - DOI - PubMed
    1. Chamekh M, Deny M, Romano M, Lefevre N, Corazza F, Duchateau J, et al. Differential susceptibility to infectious respiratory diseases between males and females linked to sex-specific innate immune inflammatory response. Front Immunol (2017) 8:1806. 10.3389/fimmu.2017.01806 - DOI - PMC - PubMed
    1. Fischer J, Jung N, Robinson N, Lehmann C. Sex differences in immune responses to infectious diseases. Infection (2015) 43(4):399–403. 10.1007/s15010-015-0791-9 - DOI - PubMed
    1. Ghosh S, Klein RS. Sex drives dimorphic immune responses to viral infections. J Immunol (2017) 198(5):1782–90. 10.4049/jimmunol.1601166 - DOI - PMC - PubMed

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