1. Bacteroides ovatus Promotes IL-22 Production and Reduces Trinitrobenzene Sulfonic Acid-Driven Colonic Inflammation.
- Author
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Ihekweazu FD, Engevik MA, Ruan W, Shi Z, Fultz R, Engevik KA, Chang-Graham AL, Freeborn J, Park ES, Venable S, Horvath TD, Haidacher SJ, Haag AM, Goodwin A, Schady DA, Hyser JM, Spinler JK, Liu Y, and Versalovic J
- Subjects
- Animals, Colitis drug therapy, Colitis metabolism, Colon drug effects, Cytokines metabolism, Dextran Sulfate metabolism, Humans, Inflammation metabolism, Intestinal Mucosa drug effects, Intestinal Mucosa metabolism, Intestines drug effects, Mice, Interleukin-22, Bacteroides drug effects, Colon metabolism, Inflammation drug therapy, Interleukins metabolism, Trinitrobenzenesulfonic Acid pharmacology
- Abstract
The intestinal microbiota influences the development and function of the mucosal immune system. However, the exact mechanisms by which commensal microbes modulate immunity is not clear. We previously demonstrated that commensal Bacteroides ovatus ATCC 8384 reduces mucosal inflammation. Herein, we aimed to identify immunomodulatory pathways employed by B. ovatus. In germ-free mice, mono-association with B. ovatus shifted the CD11b
+ /CD11c+ and CD103+ /CD11c+ dendritic cell populations. Because indole compounds are known to modulate dendritic cells, B. ovatus cell-free supernatant was screened for tryptophan metabolites by liquid chromatography-tandem mass spectrometry and larger quantities of indole-3-acetic acid were detected. Analysis of cecal and fecal samples from germ-free and B. ovatus mono-associated mice confirmed that B. ovatus could elevate indole-3-acetic acid concentrations in vivo. Indole metabolites have previously been shown to stimulate immune cells to secrete the reparative cytokine IL-22. Addition of B. ovatus cell-free supernatant to immature bone marrow-derived dendritic cells stimulated IL-22 secretion. The ability of IL-22 to drive repair in the intestinal epithelium was confirmed using a physiologically relevant human intestinal enteroid model. Finally, B. ovatus shifted the immune cell populations in trinitrobenzene sulfonic acid-treated mice and up-regulated colonic IL-22 expression, effects that correlated with decreased inflammation. Our data suggest that B. ovatus-produced indole-3-acetic acid promotes IL-22 production by immune cells, yielding beneficial effects on colitis., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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