Increased genital mucosal cytokines in Canadian women associate with higher antigen-presenting cells

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creativework.keywords - en
Inflammation
Antigen-presenting cells
Microbiome
Metaproteome
Metabolome
dc.contributor.author
Farr Zuend, Christina
Lamont, Alana
Noel-Romas, Laura
Knodel, Samantha
Birse, Kenzie
Kratzer, Kateryna
McQueen, Peter
Perner, Michelle
Ayele, Hossaena
Mutch, Sarah
Berard, Alicia R.
Schellenberg, John J.
Senturk, Faruk
McCorrister, Stuart
Westmacott, Garrett
Mulhall, Fran
Sandberg, Bonnie
Yu, Adelicia
Burnett, Margaret
Poliquin, Vanessa
Burgener, Adam D.
dc.date.accessioned
2023-10-18T15:07:25Z
dc.date.available
2023-10-18T15:07:25Z
dc.date.issued
2023-07-25
dc.description.abstract - en
BACKGROUND: 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. Video Abstract.
dc.identifier.citation
Farr Zuend, C., Lamont, A., Noel-Romas, L., Knodel, S., Birse, K., Kratzer, K., McQueen, P., Perner, M., Ayele, H., Mutch, S., Berard, A. R., Schellenberg, J. J., Senturk, F., McCorrister, S., Westmacott, G., Mulhall, F., Sandberg, B., Yu, A., Burnett, M., Poliquin, V., … Burgener, A. D. (2023). Increased genital mucosal cytokines in Canadian women associate with higher antigen-presenting cells, inflammatory metabolites, epithelial barrier disruption, and the depletion of L. crispatus. Microbiome, 11(1), 159. https://doi.org/10.1186/s40168-023-01594-y
dc.identifier.doi
https://doi.org/10.1186/s40168-023-01594-y
dc.identifier.issn
2049-2618
dc.identifier.other
PMC10367425
dc.identifier.pubmedID
37491398
dc.identifier.uri
https://open-science.canada.ca/handle/123456789/1222
dc.language.iso
en
dc.publisher
BioMed Central
dc.rights - en
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights - fr
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights.openaccesslevel - en
Gold
dc.rights.openaccesslevel - fr
Or
dc.rights.uri - en
https://creativecommons.org/licenses/by/4.0/
dc.rights.uri - fr
https://creativecommons.org/licenses/by/4.0/deed.fr
dc.subject - en
Health
dc.subject - fr
Santé
dc.subject.en - en
Health
dc.subject.fr - fr
Santé
dc.title - en
Increased genital mucosal cytokines in Canadian women associate with higher antigen-presenting cells
dc.type - en
Article
dc.type - fr
Article
local.acceptedmanuscript.articlenum
159
local.article.journalissue
1
local.article.journaltitle
Microbiome
local.article.journalvolume
11
local.peerreview - en
Yes
local.peerreview - fr
Oui
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