Sex in Immune Cells and Parasitic Diseases — A Complex Relationship

Epidemiological studies consistently show that many parasitic diseases affect males more frequently than females. These disparities are multifactorial, arising partly from gender-specific behaviors that influence exposure risk and health-seeking practices, especially in low- and middle-income countries. Increasing evidence also highlights that biological sex differences within the immune system significantly shape susceptibility to and control of parasitic infections. Recent advances combining classical immunology with single-cell transcriptomics have revealed hormonal and chromosomal factors driving sex-specific differences in innate and adaptive immune cells. These differences can critically influence the course and outcome of parasitic diseases. However, many studies on parasitic diseases still lack adequately sex-disaggregated data or fail to apply state-of-the-art immunological analyses needed to fully characterize biological sex effects. Studies in rodent models that mirror the sex bias observed in humans provide valuable tools to analyze immune mechanisms at the cellular level and dissect underlying biological differences. In this review, we summarize current knowledge on sex differences in key cellular components of innate and adaptive immunity and discuss their relevance for selected parasitic diseases of major global importance-leishmaniasis, Chagas disease, amebiasis, schistosomiasis, and malaria.