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

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.

Women for science and science for women: Gaps, challenges and opportunities towards optimizing pre-exposure prophylaxis for HIV-1 prevention

“…Semen in addition to being a carrier of HIV is also an important modulator of genital inflammation and immune activation at both the FGT ( 134 – 136 ) and the rectal mucosa ( 137 , 138 ). The production of pro-inflammatory and chemotactic cytokines is increased in the female genital mucosa in the presence of semen ( 139 – 145 ).…”

HIV–Host Cell Interactions

“…Men who have sex with men and injectable drug users are at a higher risk of HIV infection [22][23][24][25]. Body fluids such as semen, vaginal fluids and blood of infected persons contain free-floating viruses and virus-infected CD4 + -positive cells that facilitate the transmission of infection to the next cell or host [26][27][28][29].…”

Human seminal plasma stimulates the migration of CD11c+ mononuclear phagocytes to the apical side of the colonic epithelium without altering the junctional complexes in an ex vivo human intestinal model

“…Our findings can help to explain how HIV can be efficiently transmitted in such way even if the viral concentration is low. HSP is a highly immunomodulatory fluid containing several bioactive molecules with the potential to influence inflammation, immune activation (31) and is thought to disturb the physical barrier of the human colonic mucosa (32,33). We tested anti-and pro-inflammatory cytokines, chemokines and GM-CSF concentration levels of the HSP pools from HIV positive and negative donors with known fertility status to understand their role in affecting migration and permeability.…”