Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures
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 transmit...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.733619/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Elizabeth H. Byrne |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T00:23:51Z |
| format | Article |
| id | doaj.art-86849ac40fd74dae97d282ac9d69d495 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-14T00:23:51Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-86849ac40fd74dae97d282ac9d69d4952022-12-21T23:25:08ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-09-011110.3389/fcimb.2021.733619733619Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory SignaturesElizabeth H. Byrne0Elizabeth H. Byrne1Mara Farcasanu2Seth M. Bloom3Seth M. Bloom4Seth M. Bloom5Nondumiso Xulu6Jiawu Xu7Barry L. Hykes8Nomfuneko A. Mafunda9Matthew R. Hayward10Matthew R. Hayward11Mary Dong12Mary Dong13Krista L. Dong14Krista L. Dong15Krista L. Dong16Thandeka Gumbi17Thandeka Gumbi18Fransisca Xolisile Ceasar19Fransisca Xolisile Ceasar20Nasreen Ismail21Thumbi Ndung’u22Thumbi Ndung’u23Thumbi Ndung’u24Thumbi Ndung’u25Thumbi Ndung’u26Christina Gosmann27Christina Gosmann28Musie S. Ghebremichael29Musie S. Ghebremichael30Scott A. Handley31Caroline M. Mitchell32Caroline M. Mitchell33Caroline M. Mitchell34Alexandra-Chloé Villani35Alexandra-Chloé Villani36Alexandra-Chloé Villani37Douglas S. Kwon38Douglas S. Kwon39Douglas S. Kwon40Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United StatesHIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South AfricaRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesFemales Rising Through Education, Support, and Health (FRESH), Durban, South AfricaRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesFemales Rising Through Education, Support, and Health (FRESH), Durban, South AfricaFemales Rising Through Education, Support, and Health (FRESH), Durban, South AfricaHealth Systems Trust, Durban, South AfricaFemales Rising Through Education, Support, and Health (FRESH), Durban, South AfricaHealth Systems Trust, Durban, South AfricaHIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South AfricaRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesHIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute (AHRI), Durban, South AfricaMax Planck Institute for Infection Biology, Berlin, Germany0Division of Infection and Immunity, University College London, London, United KingdomRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United States1Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United States2Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States3Broad Institute of MIT and Harvard, Immunology Program, Cambridge, MA, United StatesRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fcimb.2021.733619/fullHIVfemale genital tractmicrobiomeinflammationmucosal immunologyhormonal contraception |
| spellingShingle | 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 Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures Frontiers in Cellular and Infection Microbiology HIV female genital tract microbiome inflammation mucosal immunology hormonal contraception |
| title | Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures |
| title_full | Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures |
| title_fullStr | Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures |
| title_full_unstemmed | Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures |
| title_short | Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures |
| title_sort | antigen presenting cells link the female genital tract microbiome to mucosal inflammation with hormonal contraception as an additional modulator of inflammatory signatures |
| topic | HIV female genital tract microbiome inflammation mucosal immunology hormonal contraception |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.733619/full |
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