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Review
. 2025 Jun 7;13(6):179.
doi: 10.3390/diseases13060179.

Sex Differences in Immune Responses to Infectious Diseases: The Role of Genetics, Hormones, and Aging

Pierluigi Rio  1   2 , Mario Caldarelli  1   2 , Edoardo Miccoli  1   2 , Giulia Guazzarotti  1   2 , Antonio Gasbarrini  1   2 , Giovanni Gambassi  1   2 , Rossella Cianci  1   2
Affiliations
Review

Sex Differences in Immune Responses to Infectious Diseases: The Role of Genetics, Hormones, and Aging

Pierluigi Rio et al. Diseases. .

Abstract

In recent years, gender medicine has emerged as a field of research analyzing sex-related differences in health and disease. Biological sex, depending on sex chromosome complement, sex steroid hormones, and reproductive organs, has been demonstrated to influence human susceptibility to infections, immune responses against pathogens, the clinical severity of infectious diseases, and responses to the available treatments. Men and women differ in their chromosome set, with men having one X chromosome (XY) and women two (XX). This different genetic composition results in a sex-dimorphic expression of genes and pathways involved in immune regulation, as well as in shaping immune responses to infectious agents. Moreover, estrogen, progesterone, and testosterone, impacting cells and pathways involved in both innate and adaptive immunity, have been shown to drive sex dimorphism in infectious diseases. This narrative review aims to explore the sex-related differences in responses to infections, specifically focusing on the underlying genetic and hormonal mechanisms. Hence, aging-related changes in the immune system and their potential impact on immune responses against pathogens will be discussed. Understanding sex differences and stratifying the population according to them will open the door to precision medicine and personalized patient care.

Keywords: gender medicine; genetics; hormones; immune system; infectious diseases.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Sex-related biological (genes, hormones, immune response) factors modulate the risk, severity, and outcomes of infectious diseases. Genetic inheritance (XX vs. XY) and gene status can either increase or reduce innate and adaptive immune responses. In addition, hormonal differences (estrogen, progesterone, androgens) can also enhance or decrease the activity of macrophages, neutrophils, NK, and T and B lymphocytes. The complex biological mechanism interacts with social gender, demonstrating the need for a sex- and gender-based precision medicine initiative.
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References

    1. Jit M., Cook A.R. Informing Public Health Policies with Models for Disease Burden, Impact Evaluation, and Economic Evaluation. Annu. Rev. Public Health. 2024;45:133–150. doi: 10.1146/annurev-publhealth-060222-025149. - DOI - PubMed
    1. Prem K., Cook A.R., Jit M. Projecting Social Contact Matrices in 152 Countries Using Contact Surveys and Demographic Data. PLoS Comput. Biol. 2017;13:e1005697. doi: 10.1371/journal.pcbi.1005697. - DOI - PMC - PubMed
    1. Doerre A., Doblhammer G. The Influence of Gender on COVID-19 Infections and Mortality in Germany: Insights from Age- and Gender-Specific Modeling of Contact Rates, Infections, and Deaths in the Early Phase of the Pandemic. PLoS ONE. 2022;17:e0268119. doi: 10.1371/journal.pone.0268119. - DOI - PMC - PubMed
    1. Meijs D.A.M., van Bussel B.C.T., Stessel B., Mehagnoul-Schipper J., Hana A., Scheeren C.I.E., Peters S.A.E., van Mook W.N.K.A., van der Horst I.C.C., Marx G., et al. Better COVID-19 Intensive Care Unit Survival in Females, Independent of Age, Disease Severity, Comorbidities, and Treatment. Sci. Rep. 2022;12:734. doi: 10.1038/s41598-021-04531-x. - DOI - PMC - PubMed
    1. Risman B.J. Gender as a Social Structure: Theory Wrestling with Activism. Gend. Soc. 2004;18:429–450. doi: 10.1177/0891243204265349. - DOI

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