Lymphoid-Tissue-Resident Commensal Bacteria Promote Members of the IL-10 Cytokine Family to Establish Mutualism

• Published in: Immunity (Cambridge, Mass.) Vol. 44; no. 3; pp. 634 - 646
• Main Authors: Fung, Thomas C., Bessman, Nicholas J., Hepworth, Matthew R., Kumar, Nitin, Shibata, Naoko, Kobuley, Dmytro, Wang, Kelvin, Ziegler, Carly G.K., Goc, Jeremy, Shima, Tatsuichiro, Umesaki, Yoshinori, Sartor, R. Balfour, Sullivan, Kaede V., Lawley, Trevor D., Kunisawa, Jun, Kiyono, Hiroshi, Sonnenberg, Gregory F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-03-2016; Elsevier Limited
• Subjects: Animals; Bacteria; Bordetella - immunology; Bordetella Infections - immunology; Cells, Cultured; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - microbiology; Drinking water; Genomes; Immune system; Immunology; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-22; Interleukins - genetics; Interleukins - metabolism; Intestines - immunology; Intestines - microbiology; Lymphoid Tissue - immunology; Lymphoid Tissue - microbiology; Mammals; Medical research; Metabolic disorders; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Microbiota; Phylogenetics; Receptors, Interleukin-10 - genetics; Receptors, Interleukin-10 - metabolism; Small intestine; Symbiosis - genetics; Th17 Cells - immunology; Th17 Cells - microbiology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2016.02.019

Physical separation between the mammalian immune system and commensal bacteria is necessary to limit chronic inflammation. However, selective species of commensal bacteria can reside within intestinal lymphoid tissues of healthy mammals. Here, we demonstrate that lymphoid-tissue-resident commensal bacteria (LRC) colonized murine dendritic cells and modulated their cytokine production. In germ-free and antibiotic-treated mice, LRCs colonized intestinal lymphoid tissues and induced multiple members of the IL-10 cytokine family, including dendritic-cell-derived IL-10 and group 3 innate lymphoid cell (ILC3)-derived IL-22. Notably, IL-10 limited the development of pro-inflammatory Th17 cell responses, and IL-22 production enhanced LRC colonization in the steady state. Furthermore, LRC colonization protected mice from lethal intestinal damage in an IL-10-IL-10R-dependent manner. Collectively, our data reveal a unique host-commensal-bacteria dialog whereby selective subsets of commensal bacteria interact with dendritic cells to facilitate tissue-specific responses that are mutually beneficial for both the host and the microbe.
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•Lymphoid-resident commensal bacteria (LRCs) colonize intestinal lymphoid tissues•LRCs promote tissue-specific Th17 cell and ILC3 responses in intestinal tissues•IL-22 enhances LRC colonization of intestinal lymphoid tissues•LRCs provide host tissue protection during DSS in an IL-10R-dependent manner
Commensal bacteria colonize the lumen and epithelial surface of the mammalian gastrointestinal tract. Recent reports suggest that commensal bacteria also colonize the interior of intestinal lymphoid tissues. Here, Sonnenberg and colleagues describe interactions between lymphoid-tissue-resident commensal bacteria and the host immune system during health and intestinal injury.