Authors: | Wu, W. J. H.; Kim, M.; Chang, L. C.; Assie, A.; Saldana-Morales, F. B.; Zegarra-Ruiz, D. F.; Norwood, K.; Samuel, B. S.; Diehl, G. E. |
Article Title: | Interleukin-1β secretion induced by mucosa-associated gut commensal bacteria promotes intestinal barrier repair |
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. © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. |
Keywords: | protein expression; gene sequence; sequence analysis; histopathology; nonhuman; flow cytometry; cd3 antigen; cd8 antigen; mouse; dendritic cell; interleukin 1beta; animal experiment; animal model; inflammation; cytokine; albumin; cell culture; cd11b antigen; escherichia coli; major histocompatibility antigen class 2; cell isolation; colitis; real time polymerase chain reaction; ulcerative colitis; cd4 antigen; bacterial colonization; vancomycin; intestine flora; rna 16s; bacterial dna; bacterium culture; metronidazole; bacterial infection; cd5 antigen; dna extraction; colon; cd19 antigen; interleukin 22; diphtheria toxin; complementary dna; rna extraction; feces analysis; crohn disease; bacterium isolation; interleukin 18; colony forming unit; streptomycin; neomycin; mucosa; interleukin 23; citrobacter rodentium; biological functions; ampicillin; lamina propria; microbiota; chemokine receptor cx3cr1; dextran sulfate; il-22; article; fluorochrome; bone marrow derived macrophage; colon adenocarcinoma cell line; cx3cr1+ mnps; il-1β; ilc3s; intestinal barrier repair; caco-2 cell line |
Journal Title: | Gut Microbes |
Volume: | 14 |
Issue: | 1 |
ISSN: | 1949-0976 |
Publisher: | Taylor & Francis Group |
Date Published: | 2022-01-01 |
Start Page: | 2014772 |
Language: | English |
DOI: | 10.1080/19490976.2021.2014772 |
PUBMED: | 34989321 |
PROVIDER: | scopus |
PMCID: | PMC8741296 |
DOI/URL: | |
Notes: | Article -- Export Date: 1 February 2022 -- Source: Scopus |