Gonadal Influence on Immune Responses in Malaria Infection

Sex steroids produced by the gonads exert profound effects on both innate and adaptive immunity, contributing to the well-documented sexual dimorphism in malaria outcomes. Testosterone tends to dampen inflammatory pathways and alter lymphocyte subsets, often resulting in higher parasitaemia and more severe anaemia in male hosts. By contrast, oestrogens such as 17β-oestradiol generally enhance certain cytokine responses and antibody production, which can accelerate parasite clearance but may also heighten immunopathology if unchecked. Experimental manipulations including gonadectomy and hormone replacement in rodent models of Plasmodium infection have revealed that removal of endogenous sex steroids alters splenic architecture, shifts macrophage and T-cell populations, and modifies the balance between pro-inflammatory mediators (for example interferon-γ, tumour necrosis factor-α) and anti-inflammatory signals (such as interleukin-10). These findings underscore the importance of the liver and spleen as sites where gonadal hormones shape erythropoiesis, phagocytic activity and acute phase responses. Understanding these mechanisms is crucial for development of sex-tailored vaccination strategies and for optimising therapeutic regimens in endemic regions.

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Gonadal Influence on Immune Responses in Malaria Infection publication trend

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Technical terms

Sexual dimorphism: Differences in physiology or disease susceptibility between males and females arising from genetic and hormonal factors.

Gonadectomy: Surgical removal of the testes or ovaries, used experimentally to study the absence of endogenous sex steroids.

Parasitaemia: The proportion or concentration of red blood cells infected by malaria parasites, a key measure of disease severity.

Cytokines: Small signalling proteins released by immune cells that orchestrate inflammatory and anti-inflammatory responses.

References

1. DHEA Induces Sex-Associated Differential Patterns in Cytokine and Antibody Levels in Mice Infected with Plasmodium berghei ANKA. International Journal of Molecular Sciences (2023).
2. Immunomodulatory effects of testosterone and letrozole during Plasmodium berghei ANKA infection. Frontiers in Cellular and Infection Microbiology (2023).
3. 17β-Estradiol Is Involved in the Sexual Dimorphism of the Immune Response to Malaria. Frontiers in Endocrinology (2021).
4. Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA. Frontiers in Cellular and Infection Microbiology (2022).