Research Article: Role of sex hormones and the vaginal microbiome in susceptibility and mucosal immunity to HIV-1 in the female genital tract

Date Published: September 12, 2017

Publisher: BioMed Central

Author(s): Danielle Vitali, Jocelyn M. Wessels, Charu Kaushic.

http://doi.org/10.1186/s12981-017-0169-4

Abstract

While the prevalence of Human immunodeficiency virus-1 (HIV-1) infection has stabilized globally, it continues to be the leading cause of death among women of reproductive age. The majority of new infections are transmitted heterosexually, and women have consistently been found to be more susceptible to HIV-1 infection during heterosexual intercourse compared to men. This emphasizes the need for a deeper understanding of how the microenvironment in the female genital tract (FGT) could influence HIV-1 acquisition. This short review focuses on our current understanding of the interplay between estrogen, progesterone, and the cervicovaginal microbiome and their immunomodulatory effects on the FGT. The role of hormonal contraceptives and bacterial vaginosis on tissue inflammation, T cell immunity and HIV-1 susceptibility is discussed. Taken together, this review provides valuable information for the future development of multi-purpose interventions to prevent HIV-1 infection in women.

Partial Text

Human immunodeficiency virus-1 (HIV-1) infection remains one of the most serious health challenges in the world, and the fastest growing phase of this pandemic is currently by heterosexual transmission in women [1]. Adolescent girls and young women are at particularly high risk of HIV-1 infection, accounting for 20% of new HIV-1 infections globally. The gender imbalance is even more pronounced in geographical areas with higher HIV-1 prevalence, such as sub-Saharan Africa, where women account for almost 56% of the total number of people living with HIV-1 [1]. Although the female genital mucosa is a major portal for entry of HIV-1 into the body, responsible for initiation of 40% of global HIV-1 infections, the acute events that follow HIV-1 exposure in the female genital tract (FGT) still remain unclear [2].

The FGT is a key target site for HIV-1 transmission in women, and the outcome of exposure to HIV-1 is likely determined by a number of factors that influence this mucosal microenvironment. It is unique among mucosal sites, challenged with the need to enable successful reproduction as well as mediate protection against sexually transmitted infections, such as HIV-1. Estrogen, progesterone, hormonal contraceptives and the vaginal microbiome are all factors within the microenvironment that participate in cross-talk with the immune system (Fig. 1). The net outcome of these interactions that results in an inflammatory microenvironment could be favorable for HIV-1 infection and replication by attracting target cells, which will subsequently become infected and further propagate the infection. The biological mechanisms underpinning the association between DMPA use or BV and increased HIV-1 susceptibility, although not conclusively established, likely rely on their ability to enhance mucosal inflammation and target cell recruitment within the female genital tract. A better understanding of the interplay between sex hormones, the vaginal microbiome and the immune system could inform strategies for development of multi-purpose interventions to prevent HIV-1 infection in women.Fig. 1The sex hormone-microbiome-immune system axis in the female genital tract (FGT). The hormonal milieu, consisting of estradiol and progesterone, regulates the vaginal microbiome and both these factors participate in cross-talk with the immune system in the FGT (blue), determining the level of innate inflammation in the genital tissue. Higher estrogen levels correlate with a vaginal microbiome dominated by Lactobacillus spp. which can decrease genital inflammation and reduce HIV-1 susceptibility (pink). Alternatively, the use of progestin-based contraceptives or the presence of BV can initiate an inflammatory cytokine microenvironment that attracts T cells and induce their activation (red). Elevated levels of CD4+ CCR5+ activated T cells in the tissue as a result of an inflammatory genital profile increases the risk of HIV-1 acquisition in women

 

Source:

http://doi.org/10.1186/s12981-017-0169-4

 

Leave a Reply

Your email address will not be published.