@article{659c40e0f2a4443b89feccf3f4ab1ca7,
title = "Cervicovaginal Bacteria Are a Major Modulator of Host Inflammatory Responses in the Female Genital Tract",
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.",
author = "Anahtar, {Melis N.} and Byrne, {Elizabeth H.} and Doherty, {Kathleen E.} and Bowman, {Brittany A.} and Yamamoto, {Hidemi S.} and Magali Soumillon and Nikita Padavattan and Nasreen Ismail and Amber Moodley and Sabatini, {Mary E.} and Ghebremichael, {Musie S.} and Chad Nusbaum and Curtis Huttenhower and Virgin, {Herbert W.} and Thumbi Ndung'u and Dong, {Krista L.} and Walker, {Bruce D.} and Fichorova, {Raina N.} and Kwon, {Douglas S.}",
note = "Funding Information: We would like to thank the FRESH participants; T. Cele for performing the pelvic exams; T. Sikhakhane, S. Ngcobo, and S. Zungu for clinical support; H. Shen for flow cytometric assistance; A. Lisanti for performing tissue staining; B. Corleis, C. Gosmann, and G. Olson for critical feedback and assistance; S. Karim, L. Liebenberg, N. Samsunder, and N. Garrett for helpful discussions regarding mucosal sampling; C. Monaco and S. Handley for discussions about sample preparation and sequencing; and L. Hoisington-Lopez for sequencing support. This work was supported by the Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation, the International AIDS Vaccine Initiative (IAVI) (UKZNRSA1001), and the NIAID (1R01AI111918 and RO1AI067073). D.S.K. received additional support from the Burroughs Wellcome Fund. M.N.A. was supported by award number T32GM007753 from the NIGMS, and the Paul and Daisy Soros Fellowship. R.N.F. and H.S.Y were supported by the NIAID (5R01AI079085). T.N. received additional support from the South African Research Chairs Initiative and an International Early Career Scientist Award from the Howard Hughes Medical Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIGMS or the NIH. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc..",
year = "2015",
month = may,
day = "19",
doi = "10.1016/j.immuni.2015.04.019",
language = "English",
volume = "42",
pages = "965--976",
journal = "Immunity",
issn = "1074-7613",
number = "5",
}