SeXX Matters in Infectious Disease Pathogenesis

Summary

We often use the terms “sex” and “gender” interchangeably in infectious diseases research, which is incorrect because these terms refer to different aspects of biology and behavior. The term “sex” refers to biological characteristics that define males and females, including the basic organization of chromosomes, reproductive organs, and circulating sex steroid hormone concentrations. Gender refers to the roles, behaviors, and activities that are defined by social or cultural norms, including gender norms associated with education, occupation, and health-seeking behaviors [https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005374#ppat.1005374.ref001]. If we consider infectious diseases in the context of sex and gender, then we could hypothesize that sex results in physiological differences (e.g., hormonal regulation of immune responses) that contribute to male–female differences in the control and clearance of a pathogen as well as anatomical differences that may affect exposure and transmission of a pathogen. Gender is likely associated with behaviors that influence differential exposure to pathogens. Gender also contributes to the norms that affect access to health care and health-seeking behaviors, which could influence male–female differences in the duration and severity of infection in some countries [https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005374#ppat.1005374.ref001]. By and large, both the intensity (i.e., pathogen load within an individual) and prevalence (i.e., number of infected individuals within a population) of infections are often higher for males than females, illustrating that both sex and gender play roles in male–female differences in infectious disease pathogenesis.

Key Points

• 1Sex and gender have distinct influences on infectious disease outcomes
• 2Males generally exhibit higher susceptibility to various pathogens than females
• 3Hormonal differences between sexes can affect immune response to infections
• 4Greater understanding of sex differences is crucial for improving disease treatment and research policies
• 5The inclusion of sex as a biological variable is necessary for future research in infectious disease.

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