TY - JOUR
T1 - Lymphoid-Tissue-Resident Commensal Bacteria Promote Members of the IL-10 Cytokine Family to Establish Mutualism
AU - Fung, Thomas C.
AU - Bessman, Nicholas J.
AU - Hepworth, Matthew R.
AU - Kumar, Nitin
AU - Shibata, Naoko
AU - Kobuley, Dmytro
AU - Wang, Kelvin
AU - Ziegler, Carly G.K.
AU - Goc, Jeremy
AU - Shima, Tatsuichiro
AU - Umesaki, Yoshinori
AU - Sartor, R. Balfour
AU - Sullivan, Kaede V.
AU - Lawley, Trevor D.
AU - Kunisawa, Jun
AU - Kiyono, Hiroshi
AU - Sonnenberg, Gregory F.
N1 - Funding Information:
We thank members of the Sonnenberg laboratory for discussions and critical reading of the manuscript. This research was supported by the National Institutes of Health ( DP5OD012116 , R56AI114724 , and R01AI123368 to G.F.S.), and the NIAID Mucosal Immunology Studies Team (MIST) Scholar Award in Mucosal Immunity (to G.F.S.), the Crohn’s and Colitis Foundation of America (to M.R.H.), the Cancer Research Institute Student Training and Research in Tumor Immunology grant (to T.C.F), the Wellcome Trust ( 098051 ) and Medical Research Council UK ( PF451 ) (for library preparation, sequencing and genomic analysis), the Ministry of Education, Culture, Sports and Technology of Japan (Grants-in-Aid for Scientific Research B [J.K.] and for Scientific Research S [H.K.]), the Ministry of Health and Welfare of Japan (J.K. and H.K.), Japan Science and Technology Agency (J.S.T.), Core Research for Evolutional Science and Technology (CREST) (H.K.), the National Institute of Diabetes and Digestive and Kidney Diseases ( P30-DK034987 to R.B.S.) and the Office of the Director at the National Institutes of Health ( 5-P40-OD010995 to R.B.S.). We thank Sylvester S. Roundtree Jr. (Children’s Hospital of Philadelphia) for providing clinical bacterial isolates and the National Gnotobiotic Rodent Resource Center for providing germ-free IL-10-deficient mice.
Funding Information:
We thank members of the Sonnenberg laboratory for discussions and critical reading of the manuscript. This research was supported by the National Institutes of Health (DP5OD012116, R56AI114724, and R01AI123368 to G.F.S.), and the NIAID Mucosal Immunology Studies Team (MIST) Scholar Award in Mucosal Immunity (to G.F.S.), the Crohn’s and Colitis Foundation of America (to M.R.H.), the Cancer Research Institute Student Training and Research in Tumor Immunology grant (to T.C.F), the Wellcome Trust (098051) and Medical Research Council UK (PF451) (for library preparation, sequencing and genomic analysis), the Ministry of Education, Culture, Sports and Technology of Japan (Grants-in-Aid for Scientific Research B [J.K.] and for Scientific Research S [H.K.]), the Ministry of Health and Welfare of Japan (J.K. and H.K.), Japan Science and Technology Agency (J.S.T.), Core Research for Evolutional Science and Technology (CREST) (H.K.), the National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK034987 to R.B.S.) and the Office of the Director at the National Institutes of Health (5-P40-OD010995 to R.B.S.). We thank Sylvester S. Roundtree Jr. (Children’s Hospital of Philadelphia) for providing clinical bacterial isolates and the National Gnotobiotic Rodent Resource Center for providing germ-free IL-10-deficient mice.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/3/15
Y1 - 2016/3/15
N2 - 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.
AB - 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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U2 - 10.1016/j.immuni.2016.02.019
DO - 10.1016/j.immuni.2016.02.019
M3 - Article
C2 - 26982365
AN - SCOPUS:84960341158
VL - 44
SP - 634
EP - 646
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -
