title: Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis.
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 (T(reg)) 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.
authors.affiliation: Department of Oncological Sciences, 1470 Madison Avenue, New York, NY 10029, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Mortha
authors.forename: Aleksey
authors.initials: A
authors.lastname: Chudnovskiy
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Milena
authors.initials: M
authors.lastname: Bogunovic
authors.forename: Sean P
authors.initials: SP
authors.lastname: Spencer
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D004435:Eating; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D007108:Immune Tolerance; D007113:Immunity, Innate; D053583:Interleukin-1beta / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008817:Mice, Mutant Strains; D064307:Microbiota / Q000276:immunology*; D009055:Mouth / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000941:Antigens; D053583:Interleukin-1beta; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor