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.

在小肠中，2型应答受涉及簇状细胞和2组先天淋巴样细胞（ILC2s）的信号传导回路调节。在这里，我们确定了微生物代谢物琥珀酸酯为小肠（SI）簇绒细胞的活化配体。从小肠，胆囊，结肠，胸腺和气管分离出的簇绒细胞的测序分析表明，簇绒细胞化学感应受体的表达是组织特异性的。SI簇绒细胞表达琥珀酸受体（SUCNR1），在饮用水中提供琥珀酸足以通过簇绒ILC2回路诱导多面2型免疫应答。蠕虫巴西夜蛾和三毛虫原虫都分泌琥珀酸盐作为代谢产物。体内感测毛滴虫需要SUCNR1，而巴西猪笼草是SUCNR1独立的。这些发现定义了一种簇状细胞监测微生物代谢物以启动2型免疫力并提示存在其他触发蠕虫反应的传感途径的范例。