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Immunity. 2015 May 19;42(5):965-76. doi: 10.1016/j.immuni.2015.04.019.

Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract.

Author information

1
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
2
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.
3
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
5
HIV Pathogenesis Programme, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, KwaZulu-Natal, 4001, South Africa.
6
Females Rising through Education, Support, and Health, Durban, KwaZulu-Natal, 4066, South Africa.
7
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA.
8
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
9
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
10
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; HIV Pathogenesis Programme, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, KwaZulu-Natal, 4001, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R Mandela School of Medicine, University of KwaZulu-Natal; Durban, KwaZulu-Natal, 4001, South Africa.
11
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Females Rising through Education, Support, and Health, Durban, KwaZulu-Natal, 4066, South Africa.
12
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Division of Infectious Disease, Massachusetts General Hospital, Boston, MA 02115, USA.
13
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Division of Infectious Disease, Massachusetts General Hospital, Boston, MA 02115, USA. Electronic address: dkwon@mgh.harvard.edu.

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 found that 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 in situ 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.

PMID:
25992865
PMCID:
PMC4461369
DOI:
10.1016/j.immuni.2015.04.019
[Indexed for MEDLINE]
Free PMC Article

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