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Review
. 2021 Nov;86(5):e13478.
doi: 10.1111/aji.13478. Epub 2021 Jun 16.

Semen: A modulator of female genital tract inflammation and a vector for HIV-1 transmission

Janine Jewanraj  1   2 , Sinaye Ngcapu  1   2 , Lenine J P Liebenberg  1   2
Affiliations
Review

Semen: A modulator of female genital tract inflammation and a vector for HIV-1 transmission

Janine Jewanraj et al. Am J Reprod Immunol. 2021 Nov.

Abstract

In order to establish productive infection in women, HIV must transverse the vaginal epithelium and gain access to local target cells. Genital inflammation contributes to the availability of HIV susceptible cells at the female genital mucosa and is associated with higher HIV transmission rates in women. Factors that contribute to genital inflammation may subsequently increase the risk of HIV infection in women. Semen is a highly immunomodulatory fluid containing several bioactive molecules with the potential to influence inflammation and immune activation at the female genital tract. In addition to its role as a vector for HIV transmission, semen induces profound mucosal changes to prime the female reproductive tract for conception. Still, most studies of mucosal immunity are conducted in the absence of semen or without considering its immune impact on the female genital tract. This review discusses the various mechanisms by which semen exposure may influence female genital inflammation and highlights the importance of routine screening for semen biomarkers in vaginal specimens to account for its impact on genital inflammation.

Keywords: HIV risk; cytokines; epithelial barrier integrity; female genital inflammation; immune cells; semen; vaginal microbiome.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Structure of the male genital tract. The male genital tract is made up of the penile urethra and the testes. The penile urethra is lined with a less resilient non‐keratinised pseudostratified glandular columnar epithelium and is a primary site for infection in men. The testes can be divided into two main regions, the seminiferous tubules and the interstitial spaces between the tubules. The testes are responsible for the production of testosterone and spermatogenesis
FIGURE 2
FIGURE 2
Alterations at the female genital mucosa in response to semen. (A) An optimal vaginal environment contains few cytokines and immune cells. The vaginal microbiome is dominated by Lactobacillus spp. and the mucosal barrier does not contain microabrasions. (B) The pro‐inflammatory components in semen induce cytokine production and target cell recruitment to the FGT. Semen and condomless sex may induce microabrasions in the epithelial barrier and alterations in the vaginal microbiome. (C) The anti‐inflammatory components of semen, including TGF‐β and IL‐10, are associated with fewer cervicovaginal cytokines and expansion of the Treg immune cell (CD4+CD25+) population. Additionally, since homeostasis of the vaginal microbiome is quickly restored after exposure to semen, a tolerogenic immune response to semen may be associated with minor changes in the vaginal microbiome
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