title: Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women.
abstract: Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4+T cells compared to those with Lactobacillus crispatus-dominant communities. We identified specific bacterial taxa linked with reduced (L. crispatus) or elevated (Prevotella, Sneathia, and other anaerobes) inflammation and HIV infection and found that high-risk bacteria increased numbers of activated genital CD4+T cells in a murine model. Our results suggest that highly prevalent genital bacteria increase HIV risk by inducing mucosal HIV target cells. These findings might be leveraged to reduce HIV acquisition in women living in sub-Saharan Africa.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Gosmann
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Melis N
authors.initials: MN
authors.lastname: Anahtar
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Handley
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Farcasanu
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Galeb
authors.initials: G
authors.lastname: Abu-Ali
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: 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: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Chandni
authors.initials: C
authors.lastname: Desai
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Droit
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: 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: Mary
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yuezhou
authors.initials: Y
authors.lastname: Chen
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: 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.
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; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Musie S
authors.initials: MS
authors.lastname: Ghebremichael
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Duane R
authors.initials: DR
authors.lastname: Wesemann
authors.affiliation: Vincent Obstetrics & Gynecology, Massachusetts General Hospital, Boston, MA 02115, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mitchell
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: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
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 Diseases, Massachusetts General Hospital, Boston, MA 02115, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
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; Harvard Medical School, Boston, MA 02115, USA; Division of Infectious Diseases, 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: D000818:Animals; D001421:Bacteria, Anaerobic; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002584:Cervix Uteri / Q000382:microbiology*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000382:microbiology*; D006801:Humans; D007778:Lactobacillus; D051379:Mice; D064307:Microbiota / Q000276:immunology; D018720:Prevotella; D013019:South Africa; D014621:Vagina / Q000382:microbiology*
keywords: HIV acquisition; HIV susceptibility; female genital tract (FGT); mucosal immunology; sub-Saharan Africa; vaginal microbiome