Monell Chemical Senses Center, Philadelphia, PA 19104.
Diet, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Beltsville, MD 20705.
Proc Natl Acad Sci U S A. 2018 May 22;115(21):5552-5557. doi: 10.1073/pnas.1720758115. Epub 2018 May 7.
The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 () is specifically expressed in tuft cells. Thus, we hypothesized that the succinate-Sucnr1 axis may be utilized by tuft cells to detect certain infectious agents. Here we confirmed that is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. Conventional mice with a genetic Sucnr1 deficiency () showed diminished immune responses to treatment with polyethylene glycol and streptomycin, which are known to enhance microbiota-derived succinate, but responded normally to inoculation with the parasitic worm that also produces succinate. Thus, Sucnr1 is required for microbiota-induced but not for a generalized worm-induced type 2 immunity.
2 型黏膜免疫的标志性特征包括由微绒毛细胞激活引发的肠微绒毛和杯状细胞扩张。目前尚不清楚诱导 2 型黏膜免疫的感染因子是如何被微绒毛细胞检测到的。已发表的基因芯片分析表明，琥珀酸受体 1（）特异性表达于微绒毛细胞。因此，我们假设琥珀酸- Sucnr1 轴可能被微绒毛细胞用来检测某些感染因子。本研究证实，在肠道微绒毛细胞中特异性表达，但在其他类型的肠道上皮细胞中不表达，并且表明膳食琥珀酸通过 Sucnr1 以及微绒毛细胞表达的化学感觉信号元件 gustducin 和 Trpm5 诱导微绒毛和杯状细胞增生。缺乏 Sucnr1 基因的常规小鼠（）对聚乙二醇和链霉素的治疗反应减弱，已知这两种药物可增强微生物群衍生的琥珀酸，但对寄生虫的接种反应正常，寄生虫也会产生琥珀酸。因此，Sucnr1 是微生物群诱导的，但不是一般蠕虫诱导的 2 型免疫所必需的。
