The Effects of Sex Hormones and Aging on the Mucosal Immune System in the Human Female Reproductive Tract and Implications for HIV Acquisition

Problem The female reproductive tract (FRT) is susceptible to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), which negatively impact and threaten the lives of women worldwide. While the hormonal regulation of innate and adaptive immunity in the FRT during the menstrual cycle is well‐studied, changes in mucosal immune protection throughout the FRT that occur with aging after menopause remain largely unknown. Methods This review summarizes hormonal and age‐related immune changes throughout the FRT, focusing on their effects on the function of epithelial cells and immune cells in the uterus, cervix and vagina, highlighting implications for HIV infection. Results After menopause, as reproductive function ceases, two interconnected processes, menopause and immunosenescence, drive alterations in immune protection. As women age following menopause, significant aspects of innate and adaptive immunity in the FRT are compromised in a site‐specific manner. At some FRT sites, as cell numbers decline, immunological compensation characterized by increased immunological activity is observed. Conclusions Overall, these changes in mucosal immune protection contribute to a heightened risk of STIs and HIV acquisition. Further research is essential to establish a basis for developing new therapeutic interventions to restore immune protection and mitigate conditions that endanger the health and lives of aging women.