Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis

Arthur Mortha, Aleksey Chudnovskiy, Daigo Hashimoto, Milena Bogunovic, Sean P. Spencer, Yasmine Belkaid, Miriam Merad

Research output: Contribution to journalArticle

412 Scopus citations

Abstract

The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (Treg) numbers and impaired oral tolerance. We observed that RORγt+ innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine.

Original languageEnglish (US)
Article number1249288
JournalScience
Volume343
Issue number6178
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • General

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    Mortha, A., Chudnovskiy, A., Hashimoto, D., Bogunovic, M., Spencer, S. P., Belkaid, Y., & Merad, M. (2014). Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science, 343(6178), [1249288]. https://doi.org/10.1126/science.1249288