Cervicovaginal Bacteria Are a Major Modulator of Host Inflammatory Responses in the Female Genital Tract

Melis N. Anahtar, Elizabeth H. Byrne, Kathleen E. Doherty, Brittany A. Bowman, Hidemi S. Yamamoto, Magali Soumillon, Nikita Padavattan, Nasreen Ismail, Amber Moodley, Mary E. Sabatini, Musie S. Ghebremichael, Chad Nusbaum, Curtis Huttenhower, Herbert W. Virgin, Thumbi Ndung'u, Krista L. Dong, Bruce D. Walker, Raina N. Fichorova, Douglas S. Kwon

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204 Scopus citations

Abstract

Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and foundthat the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products insitu via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman's reproductive health, including her risk of acquiring HIV.

Original languageEnglish
Pages (from-to)965-976
Number of pages12
JournalImmunity
Volume42
Issue number5
DOIs
StatePublished - May 19 2015

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    Anahtar, M. N., Byrne, E. H., Doherty, K. E., Bowman, B. A., Yamamoto, H. S., Soumillon, M., Padavattan, N., Ismail, N., Moodley, A., Sabatini, M. E., Ghebremichael, M. S., Nusbaum, C., Huttenhower, C., Virgin, H. W., Ndung'u, T., Dong, K. L., Walker, B. D., Fichorova, R. N., & Kwon, D. S. (2015). Cervicovaginal Bacteria Are a Major Modulator of Host Inflammatory Responses in the Female Genital Tract. Immunity, 42(5), 965-976. https://doi.org/10.1016/j.immuni.2015.04.019