Mucosal Immunity and HIV Acquisition in Women

Abstract

Women acquire HIV through sexual transmission. Women worldwide represent half of the people living with HIV, but young women in endemic areas are disproportionally affected. Low transmission rates per sexual act in women suggest that local immune protective mechanisms in the genital tract have the potential to prevent infection. However, conditions that induce genital inflammation are known to increase the risk of HIV acquisition. The female genital tract (FGT) is divided into different anatomical compartments with distinct reproductive functions. The immune cells present in each of these compartments are specialized in balancing reproduction and protection against infections, and are the same cells that can encounter and respond to HIV. Understanding the physiological and pathological factors that influence mucosal immune cell presence, susceptibility to HIV-infection and anti-HIV immune responses in the FGT is necessary to develop preventive strategies. Here we review recent advances in our understanding of HIV infection in the human female genital tract, with an emphasis on the characterization of the mucosal cells susceptible to HIV-infection, innate immune responses and mucosal factors that increase genital inflammation and influence susceptibility to HIV acquisition in women.

Keywords: HIV; Th17 cell; dendritic cell; female reproductive tract; genital inflammation; neutrophil.

Figure 1.. Immune cell distribution and responses in the female genital tract under healthy and inflammatory conditions.

A) The female genital tract (FGT) is divided in different anatomical compartments. The upper tract, lined by a single layer of epithelial cells, includes the endocervix, endometrium, Fallopian tubes and ovaries. The lower tract, lined with multiple layers of squamous epithelium, includes the ectocervix and vagina. B) Under physiological conditions (left panel), healthy genital tissues contain immune cells with specialized functions and unique phenotypes modified by the tissue environment. Important for HIV, immune cells including neutrophils, dendritic cells and T cells (CD8+ and CD4+ Th subsets) are present throughout the FGT in healthy women. The epithelium serves as a physical and immunological barrier, is coated with mucus, supports a Lactobacillus-dominated microbiome with anti-inflammatory and anti-HIV properties. Under inflammatory conditions (right panel), altered microbiome profiles, STIs or other exogenous factors induce the production of cytokines, chemokines and other inflammatory molecules by epithelial cells and immune cells. These cytokines and bacterial ligands recruit and activate immune cells and disrupt the epithelial barrier. These factors facilitate access of HIV to a mucosal environment rich in susceptible target cells such as Th17 cells and other CD4+ T cells expressing CCR5, increasing the likelihood for HIV acquisition.