Sex differences in neutrophil biology

Neutrophils, our frontline of defense against pathogens, exhibit pronounced sexual dimorphism in ontogeny, phenotype, and effector functions. Throughout the human lifespan, estrogen and androgen signaling, together with sex-linked genetic regulators, orchestrate neutrophil production, maturation, and immune activity, contributing to immunological differences between sexes observed across lifespan. Differences in neutrophil antimicrobial and immune responses contribute to disease susceptibility, with females having not only stronger antimicrobial defenses, but also a higher risk of autoimmunity, while males experience greater severity of infections and different cancer risks. This review summarizes and discusses the existing evidence on regulation of neutrophil biology by sex. We (1) describe the dynamics of neutrophils throughout human life in both females and males, (2) delineate sex-specific regulation of neutrophil phenotype and function, and (3) examine the significance of these differences in the susceptibility and outcomes of neutrophil-driven diseases.