Abstract
Female genital tract (FGT) inflammation increases HIV infection susceptibility. Non-optimal cervicovaginal microbiota, characterized by depletion of Lactobacillus species and increased bacterial diversity, is associated with increased FGT cytokine production. Lactobacillus species may protect against HIV partly by reducing FGT inflammation. We isolated 80 lactobacilli from South African women with non-optimal (Nugent 4–10; n = 18) and optimal microbiota (Nugent 0–3; n = 14). Cytokine production by vaginal epithelial cells in response to lactobacilli in the presence and absence of Gardnerella vaginalis was measured using Luminex. Adhesion to vaginal epithelial cells, pH, D/L-lactate production and lactate dehydrogenase relative abundance were assessed. Lactobacilli from women with non-optimal produced less lactic acid and induced greater inflammatory cytokine production than those from women with optimal microbiota, with IL-6, IL-8, IL-1α, IL-1β and MIP-1α/β production significantly elevated. Overall, lactobacilli suppressed IL-6 (adjusted p < 0.001) and IL-8 (adjusted p = 0.0170) responses to G. vaginalis. Cytokine responses to the lactobacilli were inversely associated with lactobacilli adhesion to epithelial cells and D-lactate dehydrogenase relative abundance. Thus, while cervicovaginal lactobacilli reduced the production of the majority of inflammatory cytokines in response to G. vaginalis, isolates from women with non-optimal microbiota were more inflammatory and produced less lactic acid than isolates from women with optimal microbiota.
Highlights
HIV remains a major public health concern, in sub-Saharan Africa where young South African women are at an exceptionally high risk of becoming HIV-infected[1,2]
A total of 80 Lactobacillus isolates were obtained from the cervicovaginal secretions of 32 women who participated in the Women’s Initiative in Sexual Health (WISH) study in Cape Town, South Africa [L. crispatus (n = 15), L. jensenii (n = 18), L. johnsonii (n = 5), L. mucosae (n = 19), L. plantarum (n = 2), L. ruminis (n = 5), L. salivarius (n = 2), L. vaginalis (n = 14)]
At the time of sampling, none of the participants tested positive for Treponema pallidum or had yeast infections determined by examination of Gram stained slides
Summary
HIV remains a major public health concern, in sub-Saharan Africa where young South African women are at an exceptionally high risk of becoming HIV-infected[1,2]. Bacterial vaginosis (BV) and non-optimal microbiota including Gardnerella vaginalis, Prevotella bivia, Atopobium spp., Mycoplasma hominis and Mobiluncus spp., are thought to be major drivers of FGT inflammation and HIV risk in sub-Saharan African women[7,8]. The mechanisms underlying the protective properties of non-iners Lactobacillus species that are considered to be optimal are not fully understood, it is thought that lactobacilli protect against pathogens by competitively excluding pathogen colonization, and producing antimicrobial compounds such as bacteriocins and lactic acid[24]. This study included Lactobacillus species that are considered to be optimal and are associated with the lowest levels of inflammatory cytokine production in vivo, in order to further evaluate their immunomodulatory properties that may reduce HIV risk
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