TY - JOUR
T1 - Bacteroides ovatus Promotes IL-22 Production and Reduces Trinitrobenzene Sulfonic Acid–Driven Colonic Inflammation
AU - Ihekweazu, Faith D.
AU - Engevik, Melinda A.
AU - Ruan, Wenly
AU - Shi, Zhongcheng
AU - Fultz, Robert
AU - Engevik, Kristen A.
AU - Chang-Graham, Alexandra L.
AU - Freeborn, Jasmin
AU - Park, Evelyn S.
AU - Venable, Susan
AU - Horvath, Thomas D.
AU - Haidacher, Sigmund J.
AU - Haag, Anthony M.
AU - Goodwin, Annie
AU - Schady, Deborah A.
AU - Hyser, Joseph M.
AU - Spinler, Jennifer K.
AU - Liu, Yuying
AU - Versalovic, James
N1 - Publisher Copyright:
© 2021 American Society for Investigative Pathology
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Animals
KW - Bacteroides/drug effects
KW - Colitis/drug therapy
KW - Colon/drug effects
KW - Cytokines/metabolism
KW - Dextran Sulfate/metabolism
KW - Humans
KW - Inflammation/drug therapy
KW - Interleukins/metabolism
KW - Intestinal Mucosa/drug effects
KW - Intestines/drug effects
KW - Mice
KW - Trinitrobenzenesulfonic Acid/pharmacology
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U2 - 10.1016/j.ajpath.2021.01.009
DO - 10.1016/j.ajpath.2021.01.009
M3 - Article
C2 - 33516788
AN - SCOPUS:85102810394
SN - 0002-9440
VL - 191
SP - 704
EP - 719
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -