Publication Date
1-1-2022
Journal
Gut Microbes
DOI
10.1080/19490976.2021.2014772
PMID
34989321
PMCID
PMC8741296
PubMedCentral® Posted Date
1-6-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Bacteria, Bacterial Physiological Phenomena, Colitis, Gastrointestinal Microbiome, Humans, Interleukin-18, Interleukin-1beta, Intestinal Mucosa, Macrophages, Mice, Mice, Inbred C57BL, Symbiosis, Microbiota, intestinal barrier repair, CX3CR1+ MNPS, ILC3s, IL-22, IL-1β, colitis
Abstract
The gut microbiota is essential for maintenance and repair of the intestinal epithelial barrier. As shifts in both intestinal epithelial barrier function and microbiota composition are found in inflammatory bowel disease patients, it is critical to understand the role of distinct bacteria in regulating barrier repair. We identified a mouse commensal E. coli isolate, GDAR2-2, that protects mice from Citrobacter rodentium infection and dextran sulfate sodium-induced colitis. Colonization with GDAR2-2 in mice resulted in expansion of CX3CR1+ mononuclear phagocytes, including CX3CR1+ macrophages/dendritic cells and monocytes, along with IL-22-secreting type 3 innate lymphoid cells and improved epithelial barrier function. In vitro co-culture of macrophages with GDAR2-2 resulted in IL-1β production. In vivo, protection after GDAR2-2 colonization was lost after depletion of CX3CR1+ MNPs, or blockade of IL-1β or IL-22. We further identified human commensal E. coli isolates that similarly protect mice from C. rodentium infection through CX3CR1+ MNP and IL-1β production. Together, these findings demonstrate an unexpected role for commensal bacteria in promoting IL-1β secretion to support intestinal barrier repair.
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