Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women

Christina Gosmann; Melis N Anahtar; Scott A Handley; Mara Farcasanu; Galeb Abu-Ali; Brittany A Bowman; Nikita Padavattan; Chandni Desai; Lindsay Droit; Amber Moodley; Mary Dong; Yuezhou Chen; Nasreen Ismail; Thumbi Ndung'u; Musie S Ghebremichael; Duane R Wesemann; Caroline Mitchell; Krista L Dong; Curtis Huttenhower; Bruce D Walker; Herbert W Virgin; Douglas S Kwon

doi:10.1016/j.immuni.2016.12.013

Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women

Immunity. 2017 Jan 17;46(1):29-37. doi: 10.1016/j.immuni.2016.12.013. Epub 2017 Jan 10.

Authors

Christina Gosmann¹, Melis N Anahtar¹, Scott A Handley², Mara Farcasanu³, Galeb Abu-Ali⁴, Brittany A Bowman³, Nikita Padavattan⁵, Chandni Desai², Lindsay Droit², Amber Moodley⁶, Mary Dong⁷, Yuezhou Chen⁸, Nasreen Ismail⁵, Thumbi Ndung'u⁹, Musie S Ghebremichael¹, Duane R Wesemann⁸, Caroline Mitchell¹⁰, Krista L Dong⁷, Curtis Huttenhower⁴, Bruce D Walker¹¹, Herbert W Virgin², Douglas S Kwon¹²

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Harvard Medical School, Boston, MA 02115, USA.
² Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
³ Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.
⁴ Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, 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 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.
⁸ Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁹ 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.
¹⁰ Vincent Obstetrics & Gynecology, Massachusetts General Hospital, Boston, MA 02115, USA.
¹¹ 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.
¹² 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.

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.

Keywords: HIV acquisition; HIV susceptibility; female genital tract (FGT); mucosal immunology; sub-Saharan Africa; vaginal microbiome.

Publication types

Observational Study
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Bacteria, Anaerobic
CD4-Positive T-Lymphocytes / immunology
Cervix Uteri / microbiology*
Cohort Studies
Female
Flow Cytometry
HIV Infections / microbiology*
Humans
Lactobacillus
Mice
Microbiota / immunology
Prevotella
South Africa
Vagina / microbiology*

Abstract

Publication types

MeSH terms

Grants and funding