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 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.
authors.affiliation: 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.
authors.forename: Melis N
authors.initials: MN
authors.lastname: Anahtar
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Byrne
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Doherty
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Bowman
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hidemi S
authors.initials: HS
authors.lastname: Yamamoto
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Soumillon
authors.affiliation: HIV Pathogenesis Programme, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, KwaZulu-Natal, 4001, South Africa.
authors.forename: Nikita
authors.initials: N
authors.lastname: Padavattan
authors.affiliation: HIV Pathogenesis Programme, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, KwaZulu-Natal, 4001, South Africa.
authors.forename: Nasreen
authors.initials: N
authors.lastname: Ismail
authors.affiliation: Females Rising through Education, Support, and Health, Durban, KwaZulu-Natal, 4066, South Africa.
authors.forename: Amber
authors.initials: A
authors.lastname: Moodley
authors.affiliation: Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Sabatini
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.
authors.forename: Musie S
authors.initials: MS
authors.lastname: Ghebremichael
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Nusbaum
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
authors.affiliation: 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.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: 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.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Dong
authors.affiliation: 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.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.affiliation: 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.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kwon
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa; D001419:Bacteria / Q000235:genetics / Q000276:immunology; D044822:Biodiversity; D016207:Cytokines / Q000276:immunology; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007778:Lactobacillus / Q000235:genetics / Q000276:immunology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017421:Sequence Analysis; D013019:South Africa; D014621:Vagina / Q000276:immunology* / Q000382:microbiology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D012336:RNA, Ribosomal, 16S