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- W4313368539 abstract "Abstract Crohn’s Disease (CD) has been associated with alterations in the intestinal microbiota, but the microbial mechanisms that regulate host immunity are largely unknown. We have recently shown that Adherent-Invasive E. coli (AIEC), which are enriched in CD patients, are sufficient to induce intestinal Th17 cells. Although AIEC lack pathogenic factors including type III secretion systems, many CD-derived isolates express virulence-associated metabolic enzymes including propanediol dehydratase (PduC), which enables AIEC to use fucose-derived propanediol as an alternate carbon source. We found that pduC is enriched in the microbiome and among E. coli genomes in CD patients compared to healthy controls. To evaluate the physiologic contribution of propanediol utilization to AIEC Th17 induction, we generated a pduC-deficient mutant of a CD-derived, AIEC isolate. Deletion of pduC resulted in reduced, inflammatory Th17 cells and attenuated weight loss following T cell transfer colitis. Using genetic mouse models, we found that CX3CR1+ mononuclear phagocytes are required for AIEC-mediated Th17 induction and IL-10 is required to restrain pduC-dependent colitis. Using a catalytically-inactive mutant, we determined that PduC metabolic activity was required for this immune phenotype. Cell-free supernatants from WT AIEC (but not the isogenic, pduC-deficient clone) promoted ex vivo Th17 cell polarization and metabolomics analysis (LC-MS) of these supernatants defined PduC-dependent metabolites capable of promoting Th17 polarization. These studies reveal a link between AIEC metabolism and inflammatory Th17 cells with the potential to serve as a therapeutic target in the treatment of CD." @default.
- W4313368539 created "2023-01-06" @default.
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- W4313368539 date "2020-05-01" @default.
- W4313368539 modified "2023-10-16" @default.
- W4313368539 title "Metabolic utilization of propanediol by adherent-invasive <i>E. coli</i> regulates intestinal tissue immunity" @default.
- W4313368539 doi "https://doi.org/10.4049/jimmunol.204.supp.232.7" @default.
- W4313368539 hasPublicationYear "2020" @default.
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