1. Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit
- Author
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James B. Jaffe, Jakob von Moltke, Marija S. Nadjsombati, Corey N. Miller, Lucian DiPeso, Joshua L. Pollack, Mary F. Fontana, Miranda R. Lyons-Cohen, G. A. Nagana Gowda, Mark S. Anderson, Christoph Schneider, Daniel Raftery, John W. McGinty, David J. Erle, and Richard M. Locksley
- Subjects
Male ,0301 basic medicine ,chemosensing ,Metabolite ,Succinic Acid ,Small ,Inbred C57BL ,urologic and male genital diseases ,Receptors, G-Protein-Coupled ,ILC2 ,Type 2 immune response ,Mice ,chemistry.chemical_compound ,Intestine, Small ,Receptors ,2.1 Biological and endogenous factors ,Immunology and Allergy ,Nippostrongylus brasiliensis ,Intestinal Mucosa ,Aetiology ,Receptor ,helminth ,Mice, Knockout ,Mucosal ,biology ,Innate lymphoid cell ,female genital diseases and pregnancy complications ,Intestine ,Cell biology ,Tritrichomonas ,Infectious Diseases ,medicine.anatomical_structure ,Organ Specificity ,Female ,Nippostrongylus ,Tuft cell ,protist ,Signal Transduction ,Knockout ,Immunology ,TRPM Cation Channels ,Autoimmune Disease ,Cell Line ,G-Protein-Coupled ,03 medical and health sciences ,Th2 Cells ,Species Specificity ,tuft cell ,nippostrongylus brasiliensis ,tritrichomonas ,medicine ,Animals ,Immunity, Mucosal ,Strongylida Infections ,Protozoan Infections ,Innate immune system ,urogenital system ,Inflammatory and immune system ,Immunity ,type 2 immunity ,succinate ,biology.organism_classification ,Small intestine ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,Digestive Diseases ,small intestine - Abstract
In the small intestine, type 2 responses are regulated by a signaling circuit that involves tuft cells and group 2 innate lymphoid cells (ILC2s). Here, we identified the microbial metabolite succinate as an activating ligand for small intestinal (SI) tuft cells. Sequencing analyses of tuft cells isolated from the small intestine, gall bladder, colon, thymus, and trachea revealed that expression of tuft cell chemosensory receptors is tissue specific. SI tuft cells expressed the succinate receptor (SUCNR1), and providing succinate in drinking water was sufficient to induce a multifaceted type 2 immune response via the tuft-ILC2 circuit. The helminth Nippostrongylus brasiliensis and a tritrichomonad protist both secreted succinate as a metabolite. Invivo sensing of the tritrichomonad required SUCNR1, whereas N.brasiliensis was SUCNR1 independent. These findings define a paradigm wherein tuft cells monitor microbial metabolites to initiate type 2 immunity and suggest the existence of othersensing pathways triggering the response to helminths.
- Published
- 2018
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