1. Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit.
- Author
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Nadjsombati MS, McGinty JW, Lyons-Cohen MR, Jaffe JB, DiPeso L, Schneider C, Miller CN, Pollack JL, Nagana Gowda GA, Fontana MF, Erle DJ, Anderson MS, Locksley RM, Raftery D, and von Moltke J
- Subjects
- Animals, Cell Line, Female, Intestinal Mucosa metabolism, Intestine, Small drug effects, Intestine, Small immunology, Male, Mice, Inbred C57BL, Mice, Knockout, Nippostrongylus drug effects, Nippostrongylus immunology, Nippostrongylus metabolism, Organ Specificity, Protozoan Infections immunology, Receptors, G-Protein-Coupled immunology, Signal Transduction immunology, Species Specificity, Strongylida Infections immunology, TRPM Cation Channels metabolism, Th2 Cells immunology, Tritrichomonas drug effects, Tritrichomonas immunology, Tritrichomonas metabolism, Immunity, Mucosal drug effects, Intestinal Mucosa cytology, Intestinal Mucosa immunology, Receptors, G-Protein-Coupled metabolism, Signal Transduction drug effects, Succinic Acid pharmacology
- 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. In vivo 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 other sensing pathways triggering the response to helminths., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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