Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT). During parasite infection, mice with epithelial-specific deletion of ChAT had increased worm burden, fitness, and fecal egg counts, even though type 2 immune responses were comparable. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. Finally, we demonstrated a direct effect of ACh on worms, which reduced their fecundity via helminth-expressed muscarinic ACh receptors. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infection provides an additional type 2 immune response effector function.

寄生虫感染后，活化的肠道簇细胞会分泌白细胞介素 25 (IL-25)，从而启动 2 型免疫反应，在此期间固有层2 型先天淋巴细胞 (ILC2) 会产生 IL-13。这会导致上皮重塑，包括簇细胞增生，其功能尚不清楚。我们鉴定了簇细胞的胆碱能效应功能，簇细胞是唯一表达胆碱乙酰转移酶（ChAT）的上皮细胞。在寄生虫感染期间，尽管 2 型免疫反应相当，但上皮特异性 ChAT 缺失的小鼠的蠕虫负担、健康状况和粪便卵数均有所增加。从机制上讲，IL-13 扩增的簇细胞将乙酰胆碱 (ACh) 释放到肠腔中。最后，我们证明了乙酰胆碱对蠕虫的直接影响，通过蠕虫表达的毒蕈碱乙酰胆碱受体降低了它们的繁殖力。因此，簇细胞是幼鼠体内的前哨细胞，它们在蠕虫感染后的扩增提供了额外的 2 型免疫反应效应功能。