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.
Highlights
Respiratory virus infections lead to significant health problems worldwide [1]
Future work will determine if this numerical disparity in ILC2s leads to sex differences in the resolution of respiratory virus infection
Sex differences in immunity to respiratory viruses are evident in humans and experimental rodent models
Summary
Humans show marked sex differences in the severity, prevalence, and outcome of inflammatory lung diseases including viral infection [2, 3]. Innate immune responses have crucial roles in early defense against viruses and shape antigen-specific adaptive immune responses and promote tissue repair. A number of recent reviews highlight sex differences in innate immune pathways during infectious disease [4,5,6]. We review literature reports on the sex differences in numbers and functional responses of innate immune cells in the lung and their regulation by sex hormones in homeostasis and during viral lung infection. We highlight ways in which sex differences in innate cells may influence both the proinflammatory/effector phase and the resolution/tissue repair phase important in the host response to respiratory virus infection (Figure 1)
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