The role of bacterial vaginosis and trichomonas in HIV transmission across the female genital tract

Abstract

Bacterial vaginosis (BV) and Trichomonas vaginalis (TV) infections are both very common and are associated with increased risk of sexual transmission of HIV. There are several mechanisms by which BV and TV could affect susceptibility including inducing pro-inflammatory cytokines and disrupting mucosal barrier function. This review highlights recent advances in our understanding of how these genital conditions lead to an increased risk of HIV infection in women.

Fig. (1). Lower Genital Tract Bacterial Microbiota of a group of US Women

Samples were obtained by cervicovaginal lavage from 10 women without BV (left) and 10 with BV (right). Note that BV tends to be polymicrobial while microbiota of non-BV tends to be nearly all lactobacilli. Microbiota was determined by pyrosequencing of the 16S rRNA gene and inputting the sequences into Ribosomal Database 10.

Fig. (2). Lower Genital Tract Bacterial Microbiota of Female Macaques

Samples were provided by Ellen Kersh from ten pigtailed macaques at the Centers for Disease Control and Prevention, by Ron Veazey from nine rhesus macaques from the Tulane National Primate Research Center and by Chris Miller from 11 rhesus macaques at the California National Primate Research Center at UC Davis. Note that the macaque microbiota at these three primate centers has similarities to BV in humans. Microbiota was determined by pyrosequencing of the 16S rRNA gene and inputting the sequencing into Ribosomal Database 10.

Fig. (3). Bacterial Vaginosis Increases Levels of Proinflammatory Cytokines in the Lower Genital Tract

Cervicovaginal lavage samples were obtained from women with no STDs and women with BV and no other STDs. IL-β, IL-8, and CXCL9 levels were measured utilizing Cytometric Bead Arrays (BD Biosciences). To detect lactoferrin, custom cytometric bead arrays were made by coupling blank beads with rabbit antibody to lactoferrin. All bead arrays were assayed on a FacsCalibur and levels of cytokines calculated using BD CBA software (BD Biosciences [106]).

Fig. (4). Butyric Acid Induces Production of IL-1β

Peripheral blood mononuclear cells (PBMCs) obtained from healthy donors were incubated with either LPS (1 μg/ml), butyric acid (BA, 20 mM), acetic acid (AA, 20 mM) or medium only (no stim) for 4 hours in the presence of GolgiPlug (BD Biosciences). Cells were washed and stained with an antibody to CD14. They were then fixed, permeablized, and stained with an antibody to IL-1β. Events were collected on a FacsCalibur and analyzed using CellQuest software (BD Biosciences). Total PBMCs were gated by light scatter. This figure shows that the CD14-positive monocyte population in PBMCs, but not CD14-negative lymphocytes, are induced by butyric acid to produce IL-1β.

Fig. (5). Butyric Acid, But Not Acetic Acid, Suppresses HIV Infection of Macrophages

Monocytes were obtained by adherence from PBMCs and differentiated into macrophages by culture in Monocyte Colony Stimulating Factor (M-CSF) for seven days. Left panel: Cells were treated with SCFAs for 16 hours, washed, and infected with HIVBaL for 16 hours. Levels of HIV provirus in cells relative to GAPDH were then determined. Right panel: Cells were infected for 4 hours, washed and treated with SCFAs for 16 hours. After washing, cells were cultured 12 days and culture supernatant HIV p24 levels measured.