Immunity:微生物生成的琥珀酸,引起肠道免疫应答
  • 小肠中,簇细胞和2型天然淋巴细胞(ILC2)形成的信号回路调控2型免疫应答;
  • 小肠、胆囊、结肠、胸腺和气管中的簇细胞具有组织特异的化学感受受体;
  • 小肠簇细胞表达琥珀酸受体(SUCNR1),通过饮水让小鼠摄入琥珀酸,足以经簇细胞-ILC2回路诱导多层面的2型免疫应答,包括ILC2活化、簇细胞和杯状细胞增生、嗜酸粒细胞增多;
  • 三毛滴虫和巴西日圆线虫均可生成代谢物琥珀酸,二者分别通过SUCNR1依赖和非依赖的机制,被肠道免疫感知。
主编推荐语
mildbreeze
簇细胞被认为是免疫系统在多个组织中的“侦察兵”,Immunity上的一项最新研究表明,小肠中的簇细胞可感知微生物代谢的琥珀酸,从而诱导2型免疫应答。可以与此前Cell发表的相关研究(查看文章)搭配阅读。
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
图片
Immunity [IF:22.553]

Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit

肠道簇细胞对琥珀酸的察觉触发了2型天然免疫回路

10.1016/j.immuni.2018.06.016

2018-07-17, Article

Abstract & Authors:展开

Abstract:收起
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.

First Authors:
Marija S Nadjsombati,John W McGinty

Correspondence Authors:
Jakob von Moltke

All Authors:
Marija S Nadjsombati,John W McGinty,Miranda R Lyons-Cohen,James B Jaffe,Lucian DiPeso,Christoph Schneider,Corey N Miller,Joshua L Pollack,G A Nagana Gowda,Mary F Fontana,David J Erle,Mark S Anderson,Richard M Locksley,Daniel Raftery,Jakob von Moltke

评论