TY - JOUR
T1 - Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures
AU - Byrne, Elizabeth H.
AU - Farcasanu, Mara
AU - Bloom, Seth M.
AU - Xulu, Nondumiso
AU - Xu, Jiawu
AU - Hykes, Barry L.
AU - Mafunda, Nomfuneko A.
AU - Hayward, Matthew R.
AU - Dong, Mary
AU - Dong, Krista L.
AU - Gumbi, Thandeka
AU - Ceasar, Fransisca Xolisile
AU - Ismail, Nasreen
AU - Ndung’u, Thumbi
AU - Gosmann, Christina
AU - Ghebremichael, Musie S.
AU - Handley, Scott A.
AU - Mitchell, Caroline M.
AU - Villani, Alexandra Chloé
AU - Kwon, Douglas S.
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) grants R01AI111918 and Bill and Melinda Gates Foundation grant OPP1189208 to DK and HU CFAR NIH/NAIDS 5P30AI060354-15 to SB. EB was supported by award number T32GM007753 from the National Institute of General Medical Sciences. SB was supported in part by NIH grant T32 AI007387.
Funding Information:
We thank study participants for the donation of clinical samples, study staff at the FRESH cohort, and processing laboratory staff at HPP in Durban, H. Shen and P. Ramkalawon at AHRI and M. Waring at the Ragon Institute for assistance with cell sorting, and B.A. Bowman for her invaluable assistance in data collection.
Publisher Copyright:
© Copyright © 2021 Byrne, Farcasanu, Bloom, Xulu, Xu, Hykes, Mafunda, Hayward, Dong, Dong, Gumbi, Ceasar, Ismail, Ndung’u, Gosmann, Ghebremichael, Handley, Mitchell, Villani and Kwon.
PY - 2021/9/16
Y1 - 2021/9/16
N2 - 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.
AB - 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.
KW - HIV
KW - female genital tract
KW - hormonal contraception
KW - host-microbiome interaction
KW - inflammation
KW - microbiome
KW - mucosal immunology
UR - http://www.scopus.com/inward/record.url?scp=85116329180&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2021.733619
DO - 10.3389/fcimb.2021.733619
M3 - Article
C2 - 34604114
AN - SCOPUS:85116329180
SN - 2235-2988
VL - 11
JO - Frontiers in cellular and infection microbiology
JF - Frontiers in cellular and infection microbiology
M1 - 733619
ER -