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Sexual Dimorphism in Innate Immunity

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Abstract

Sexual dimorphisms account for differences in clinical manifestations or incidence of infectious or autoimmune diseases and malignancy between females and males. Females develop enhanced innate and adaptive immune responses than males and are less susceptible to many infections of bacterial, viral, parasitic, and fungal origin and malignancies but in contrast, they are more prone to develop autoimmune diseases. The higher susceptibility to infections in males is observed from birth to adulthood, suggesting that sex chromosomes and not sex hormones have a major role in sexual dimorphism in innate immunity. Sex-based regulation of immune responses ultimately contributes to age-related disease development and life expectancy. Differences between males and females have been described in the expression of pattern recognition receptors of the innate immune response and in the functional responses of phagocytes and antigen presenting cells. Different factors have been shown to account for the sex-based disparity in immune responses, including genetic factors and hormonal mediators, which contribute independently to dimorphism in the innate immune response. For instance, several genes encoding for innate immune molecules are located on the X chromosome. In addition, estrogen and/or testosterone have been reported to modulate the differentiation, maturation, lifespan, and effector functions of innate immune cells, including neutrophils, macrophages, natural killer cells, and dendritic cells. In this review, we will focus on differences between males and females in innate immunity, which represents the first line of defense against pathogens and plays a fundamental role in the activation, regulation, and orientation of the adaptive immune response.

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Funding

The contribution of Ministero della Salute (RF-2013-02355470), Ministry of Education, University and Research (PRIN 2015YYKPNN), and the Associazione Italiana Ricerca sul Cancro (MFAG 2016 ID 18475) is gratefully acknowledged.

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Jaillon, S., Berthenet, K. & Garlanda, C. Sexual Dimorphism in Innate Immunity. Clinic Rev Allerg Immunol 56, 308–321 (2019). https://doi.org/10.1007/s12016-017-8648-x

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