Lymphoid tissue-resident commensal bacteria promote members of the IL-10 cytokine family to establish mutualism

Summary

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-associated lymphoid tissues of healthy mammals. Here, we demonstrate that lymphoid tissue-resident commensal bacteria (LRC) colonized murine dendritic cells and modulate their cytokine production. In germ-free and antibiotic-treated mice, LRCs colonized intestinal-associated 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 dialogue 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.

Graphical abstract