Tuft cells are a type of intestinal epithelial cells that exist in epithelial barriers and play a critical role in immunity against parasite infection. It remains insufficiently clear whether Tuft cells participate in bacterial eradication. Here, we identified Sh2d6 as a signature marker for CD45⁺ Tuft-2 cells. Depletion of Tuft-2 cells resulted in susceptibility to bacterial infection. Tuft-2 cells quickly expanded in response to bacterial infection and sensed the bacterial metabolite N-undecanoylglycine through vomeronasal receptor Vmn2r26. Mechanistically, Vmn2r26 engaged with N-undecanoylglycine activated G-protein-coupled receptor-phospholipase C gamma2 (GPCR-PLCγ2)-Ca²⁺ signaling axis, which initiated prostaglandin D2 (PGD2) production. PGD2 enhanced the mucus secretion of goblet cells and induced antibacterial immunity. Moreover, Vmn2r26 signaling also promoted SpiB transcription factor expression, which is responsible for Tuft-2 cell development and expansion in response to bacterial challenge. Our findings reveal an additional function of Tuft-2 cells in immunity against bacterial infection through Vmn2r26-mediated recognition of bacterial metabolites.

簇绒细胞是一种肠上皮细胞，存在于上皮屏障中，在抵抗寄生虫感染的免疫中起关键作用。塔夫特细胞是否参与细菌根除仍然不够清楚。在这里，我们将 Sh2d6 鉴定为 CD45 ⁺ Tuft-2 细胞的特征标记。Tuft-2 细胞的消耗导致对细菌感染的易感性。Tuft-2 细胞响应细菌感染迅速扩增，并通过犁鼻受体 Vmn2r26 感知细菌代谢物 N-十一烷酰甘氨酸。机制上，Vmn2r26 与 N-十一烷酰甘氨酸激活的 G 蛋白偶联受体-磷脂酶 C γ2 (GPCR-PLCγ2)-Ca ^2+结合信号轴，它启动了前列腺素 D2 (PGD2) 的产生。PGD​​2增强杯状细胞粘液分泌并诱导抗菌免疫。此外，Vmn2r26 信号还促进了 SpiB 转录因子的表达，该转录因子负责 Tuft-2 细胞在应对细菌挑战时的发育和扩增。我们的研究结果揭示了 Tuft-2 细胞通过 Vmn2r26 介导的细菌代谢物识别在抵抗细菌感染方面的额外功能。