Sex Differences in Immune Responses to Infectious Diseases: The Role of Genetics, Hormones, and Aging

In recent years, gender medicine has emerged as a field of research analyzing sex-related differences in health and disease. Biological sex, depending on sex chromosome complement, sex steroid hormones, and reproductive organs, has been demonstrated to influence human susceptibility to infections, immune responses against pathogens, the clinical severity of infectious diseases, and responses to the available treatments. Men and women differ in their chromosome set, with men having one X chromosome (XY) and women two (XX). This different genetic composition results in a sex-dimorphic expression of genes and pathways involved in immune regulation, as well as in shaping immune responses to infectious agents. Moreover, estrogen, progesterone, and testosterone, impacting cells and pathways involved in both innate and adaptive immunity, have been shown to drive sex dimorphism in infectious diseases. This narrative review aims to explore the sex-related differences in responses to infections, specifically focusing on the underlying genetic and hormonal mechanisms. Hence, aging-related changes in the immune system and their potential impact on immune responses against pathogens will be discussed. Understanding sex differences and stratifying the population according to them will open the door to precision medicine and personalized patient care.