Bacterial Vaginosis Is Associated with Loss of Gamma Delta T Cells in the Female Reproductive Tract in Women in the Miami Women Interagency HIV Study (WIHS): A Cross Sectional Study.

Maria L Alcaide,Deborah L Jones,Violeta J Rodriguez,Eckhard R Podack,Laura Romero,Octavio Martinez,Kristopher Arheart,Natasa Strbo,Hector Bolivar,Margaret A Fischl,David N Fredricks

doi:10.1371/journal.pone.0153045

Abstract

Bacterial vaginosis (BV) is the most common female reproductive tract infection and is associated with an increased risk of acquiring and transmitting HIV by a mechanism that is not well understood. Gamma delta (GD) T cells are essential components of the adaptive and innate immune system, are present in the female reproductive tract, and play an important role in epithelial barrier protection. GD1 cells predominate in the mucosal tissue and are important in maintaining mucosal integrity. GD2 cells predominate in peripheral blood and play a role in humoral immunity and in the immune response to pathogens. HIV infection is associated with changes in GD T cells frequencies in the periphery and in the female reproductive tract. The objective of this study is to evaluate if changes in vaginal flora occurring with BV are associated with changes in endocervical GD T cell responses, which could account for increased susceptibility to HIV. Seventeen HIV-infected (HIV+) and 17 HIV-uninfected (HIV-) pre-menopausal women underwent collection of vaginal swabs and endocervical cytobrushes. Vaginal flora was assessed using the Nugent score. GD T cells were assessed in cytobrush samples by flow cytometry. Median Nugent score was 5.0 and 41% of women had abnormal vaginal flora. In HIV uninfected women there was a negative correlation between Nugent score and cervical GD1 T cells (b for interaction = - 0.176, p<0.01); cervical GD1 T cells were higher in women with normal vaginal flora than in those with abnormal flora (45.00% vs 9.95%, p = 0.005); and cervical GD2 T cells were higher in women with abnormal flora than in those with normal flora (1.70% vs 0.35%, p = 0.023). GD T cells in the genital tract are protective (GD1) and are targets for HIV entry (GD2). The decrease in cervical GD1 and increase in GD2 T cells among women with abnormal vaginal flora predisposes women with BV to HIV acquisition. We propose to use GD T cell as markers of female genital tract vulnerability to HIV.

Highlights

Bacterial Vaginosis (BV) is the most common female reproductive tract (FRT) infection and occurs in up to 40% of women at risk of or infected with the Human Immunodeficiency Virus (HIV) [1,2,3,4,5]
Exploratory analyses were done to evaluate if the frequencies of GD1 or GD2 T cells were associated with CD4 counts or plasma viremia in women with HIV infection
Association between the frequency of GD1 or GD2 T cells and CD4 counts or plasma viremia. In this pilot study we evaluated the relationship between changes in the vaginal flora and endocervical gamma delta (GD) T cells among women enrolled in the Miami Women Interagency HIV Study (WIHS)

Summary

Introduction

Bacterial Vaginosis (BV) is the most common female reproductive tract (FRT) infection and occurs in up to 40% of women at risk of or infected with the Human Immunodeficiency Virus (HIV) [1,2,3,4,5]. BV increases the risk of sexually transmitted infections (STI), HIV acquisition and HIV transmission to male sex partners and newborns [8,9,10,11,12,13]. The risk factors for developing BV and the mechanisms underlying the association between BV, STI and HIV remain largely unknown. Epidemiological and clinical studies have identified associations between BV and other factors, including African American ethnicity, intravaginal douching, new sexual partners, multiple sex partners, and unprotected vaginal intercourse [14, 15]. Mechanisms by which risk factors are linked with the occurrence of BV and by which BV increases FRT vulnerability to HIV and STI have not been been completely elucidated

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