Female reproductive status and ecological conditions impact the magnitude of sex differences in human immune status across the lifespan

Current research indicates that women experience lower infectious disease burden and elevated risk of autoimmunity relative to men. Most research, however, is limited to industrialized urban populations and often excludes women in different reproductive phases. We examine age-specific sexual dimorphism in leukocyte differential and neutrophil-to-lymphocyte ratio (NLR), stratified by female reproductive status, among the Tsimane (n = 5,866), a natural-fertility non-industrialized population, and the USA (n = 9,825). We show that sex differences in immune measures across the lifespan are generally lower among the Tsimane (a natural-fertility non-industrialized population) compared to the USA, primarily due to population-specific effects of age and parity on female immune status during pregnancy. Neutrophil-to-lymphocyte ratio, a marker of systemic inflammation, is acutely elevated during pregnancy among primiparous women in the USA, suggesting that later age at first birth and reduced parity may contribute to excess autoimmune disease among women by altering the immunological legacy of pregnancy.