Increased genital mucosal cytokines in Canadian women associate with higher antigen-presenting cells, inflammatory metabolites, epithelial barrier disruption, and the depletion of L. crispatus

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dc.contributor.authorFarr Zuend, Christina
dc.contributor.authorLamont, Alana
dc.contributor.authorNoel-Romas, Laura
dc.contributor.authorKnodel, Samantha
dc.contributor.authorBirse, Kenzie
dc.contributor.authorKratzer, Kateryna
dc.contributor.authorMcQueen, Peter
dc.contributor.authorPerner, Michelle
dc.contributor.authorAyele, Hossaena
dc.contributor.authorMutch, Sarah
dc.contributor.authorBerard, Alicia R.
dc.contributor.authorSchellenberg, John J.
dc.contributor.authorSenturk, Faruk
dc.contributor.authorMcCorrister, Stuart
dc.contributor.authorWestmacott, Garrett
dc.contributor.authorMulhall, Fran
dc.contributor.authorSandberg, Bonnie
dc.contributor.authorYu, Adelicia
dc.contributor.authorBurnett, Margaret
dc.contributor.authorPoliquin, Vanessa
dc.contributor.authorBurgener, Adam D.
dc.date.accessioned2023-11-07T18:21:18Z
dc.date.available2023-11-07T18:21:18Z
dc.date.issued2023-07-25
dc.date.updated2023-11-03T09:18:14Z
dc.description.abstractBackground Cervicovaginal inflammation has been linked to negative reproductive health outcomes including the acquisition of HIV, other sexually transmitted infections, and cervical carcinogenesis. While changes to the vaginal microbiome have been linked to genital inflammation, the molecular relationships between the functional components of the microbiome with cervical immunology in the reproductive tract are understudied, limiting our understanding of mucosal biology that may be important for reproductive health. Results In this study, we used a multi’-omics approach to profile cervicovaginal samples collected from 43 Canadian women to characterize host, immune, functional microbiome, and metabolome features of cervicovaginal inflammation. We demonstrate that inflammation is associated with lower amounts of L. crispatus and higher levels of cervical antigen-presenting cells (APCs). Proteomic analysis showed an upregulation of pathways related to neutrophil degranulation, complement, and leukocyte migration, with lower levels of cornified envelope and cell-cell adherens junctions. Functional microbiome analysis showed reductions in carbohydrate metabolism and lactic acid, with increases in xanthine and other metabolites. Bayesian network analysis linked L. crispatus with glycolytic and nucleotide metabolism, succinate and xanthine, and epithelial proteins SCEL and IVL as major molecular features associated with pro-inflammatory cytokines and increased APCs. Conclusions This study identified key molecular and immunological relationships with cervicovaginal inflammation, including higher APCs, bacterial metabolism, and proteome alterations that underlie inflammation. As APCs are involved in HIV transmission, parturition, and cervical cancer progression, further studies are needed to explore the interactions between these cells, bacterial metabolism, mucosal immunity, and their relationship to reproductive health.
dc.identifier.citationMicrobiome. 2023 Jul 25;11(1):159
dc.identifier.doi10.1186/s40168-023-01594-y
dc.identifier.urihttp://hdl.handle.net/1993/37768
dc.language.isoeng
dc.language.rfc3066en
dc.publisherBMC
dc.rightsopen accessen_US
dc.rights.holderThe Author(s)
dc.subjectInflammation
dc.subjectAntigen‑presenting cells
dc.subjectMicrobiome
dc.subjectMetaproteome
dc.subjectMetabolome
dc.titleIncreased genital mucosal cytokines in Canadian women associate with higher antigen-presenting cells, inflammatory metabolites, epithelial barrier disruption, and the depletion of L. crispatus
dc.typeJournal Article
local.author.affiliationRady Faculty of Health Sciences::Max Rady College of Medicine::Department of Medical Microbiology and Infectious Diseases
oaire.awardNumberHB3‑164066
oaire.awardTitleInnovative Biomedical and Clinical HIV/AIDS Research: Team grant
oaire.citation.issue159
oaire.citation.titleMicrobiome
oaire.citation.volume11
project.funder.identifierhttps://doi.org/10.13039/501100000024
project.funder.nameCanadian Institutes of Health Research
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