肠簇细胞通过检测琥珀酸触发 2 型先天免疫回路。
Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit.
机构信息
Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Immunity. 2018 Jul 17;49(1):33-41.e7. doi: 10.1016/j.immuni.2018.06.016.
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 型反应受涉及绒毛细胞和 2 型固有淋巴细胞 (ILC2) 的信号通路调控。在这里，我们鉴定出微生物代谢产物琥珀酸作为小肠 (SI) 绒毛细胞的激活配体。从小肠、胆囊、结肠、胸腺和气管中分离的绒毛细胞的测序分析表明，绒毛细胞化学感觉受体的表达具有组织特异性。SI 绒毛细胞表达琥珀酸受体 (SUCNR1)，并且在饮水中提供琥珀酸足以通过绒毛细胞-ILC2 回路诱导多方面的 2 型免疫反应。寄生虫旋毛虫和一种三鞭毛虫原生动物都分泌琥珀酸作为代谢物。在体内感知三鞭毛虫需要 SUCNR1，而 N. brasiliensis 则不需要 SUCNR1。这些发现定义了一个范例，其中绒毛细胞监测微生物代谢物以启动 2 型免疫，并表明存在其他触发对寄生虫反应的感应途径。
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