Frontiers in Cellular and Infection Microbiology (Sep 2021)
Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures
- Elizabeth H. Byrne,
- Elizabeth H. Byrne,
- Mara Farcasanu,
- Seth M. Bloom,
- Seth M. Bloom,
- Seth M. Bloom,
- Nondumiso Xulu,
- Jiawu Xu,
- Barry L. Hykes,
- Nomfuneko A. Mafunda,
- Matthew R. Hayward,
- Matthew R. Hayward,
- Mary Dong,
- Mary Dong,
- Krista L. Dong,
- Krista L. Dong,
- Krista L. Dong,
- Thandeka Gumbi,
- Thandeka Gumbi,
- Fransisca Xolisile Ceasar,
- Fransisca Xolisile Ceasar,
- Nasreen Ismail,
- Thumbi Ndung’u,
- Thumbi Ndung’u,
- Thumbi Ndung’u,
- Thumbi Ndung’u,
- Thumbi Ndung’u,
- Christina Gosmann,
- Christina Gosmann,
- Musie S. Ghebremichael,
- Musie S. Ghebremichael,
- Scott A. Handley,
- Caroline M. Mitchell,
- Caroline M. Mitchell,
- Caroline M. Mitchell,
- Alexandra-Chloé Villani,
- Alexandra-Chloé Villani,
- Alexandra-Chloé Villani,
- Douglas S. Kwon,
- Douglas S. Kwon,
- Douglas S. Kwon
Affiliations
- Elizabeth H. Byrne
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Elizabeth H. Byrne
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Mara Farcasanu
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Seth M. Bloom
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Seth M. Bloom
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Seth M. Bloom
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States
- Nondumiso Xulu
- HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa
- Jiawu Xu
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Barry L. Hykes
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
- Nomfuneko A. Mafunda
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Matthew R. Hayward
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Matthew R. Hayward
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Mary Dong
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Mary Dong
- Females Rising Through Education, Support, and Health (FRESH), Durban, South Africa
- Krista L. Dong
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Krista L. Dong
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Krista L. Dong
- Females Rising Through Education, Support, and Health (FRESH), Durban, South Africa
- Thandeka Gumbi
- Females Rising Through Education, Support, and Health (FRESH), Durban, South Africa
- Thandeka Gumbi
- Health Systems Trust, Durban, South Africa
- Fransisca Xolisile Ceasar
- Females Rising Through Education, Support, and Health (FRESH), Durban, South Africa
- Fransisca Xolisile Ceasar
- Health Systems Trust, Durban, South Africa
- Nasreen Ismail
- HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa
- Thumbi Ndung’u
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Thumbi Ndung’u
- HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa
- Thumbi Ndung’u
- Africa Health Research Institute (AHRI), Durban, South Africa
- Thumbi Ndung’u
- Max Planck Institute for Infection Biology, Berlin, Germany
- Thumbi Ndung’u
- 0Division of Infection and Immunity, University College London, London, United Kingdom
- Christina Gosmann
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Christina Gosmann
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Musie S. Ghebremichael
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Musie S. Ghebremichael
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Scott A. Handley
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
- Caroline M. Mitchell
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Caroline M. Mitchell
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Caroline M. Mitchell
- 1Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, United States
- Alexandra-Chloé Villani
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Alexandra-Chloé Villani
- 2Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States
- Alexandra-Chloé Villani
- 3Broad Institute of MIT and Harvard, Immunology Program, Cambridge, MA, United States
- Douglas S. Kwon
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United States
- Douglas S. Kwon
- Department of Medicine, Harvard Medical School, Boston, MA, United States
- Douglas S. Kwon
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States
- DOI
- https://doi.org/10.3389/fcimb.2021.733619
- Journal volume & issue
-
Vol. 11
Abstract
The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low Lactobacillus abundance are associated with a number of adverse reproductive outcomes, such as preterm birth, cervical dysplasia, and sexually transmitted infections (STIs), including HIV. Vaginal dysbiosis is associated with local mucosal inflammation, which likely serves as a biological mediator of poor reproductive outcomes. Yet the precise mechanisms of this FGT inflammation remain unclear. Studies in humans have been complicated by confounding demographic, behavioral, and clinical variables. Specifically, hormonal contraception is associated both with changes in the vaginal microbiome and with mucosal inflammation. In this study, we examined the transcriptional landscape of cervical cell populations in a cohort of South African women with differing vaginal microbial community types. We also investigate effects of reproductive hormones on the transcriptional profiles of cervical cells, focusing on the contraceptive depot medroxyprogesterone acetate (DMPA), the most common form of contraception in sub-Saharan Africa. We found that antigen presenting cells (APCs) are key mediators of microbiome associated FGT inflammation. We also found that DMPA is associated with significant transcriptional changes across multiple cell lineages, with some shared and some distinct pathways compared to the inflammatory signature seen with dysbiosis. These results highlight the importance of an integrated, systems-level approach to understanding host-microbe interactions, with an appreciation for important variables, such as reproductive hormones, in the complex system of the FGT mucosa.
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