Abstract:
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.
摘要:
寄生虫感染后,活化的肠簇状细胞分泌白细胞介素-25(IL-25),其启动2型免疫应答,在此期间固有层2型先天淋巴样细胞(ILC2s)产生IL-13。这会导致上皮重塑,包括簇绒细胞增生,它的功能是未知的。我们确定了簇绒细胞的胆碱能效应功能,它们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,ChAT上皮特异性缺失的小鼠增加了蠕虫负担,健身,和粪便卵数,即使2型免疫反应相当。机械上,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ACh对蠕虫的直接作用,通过蠕虫表达的毒蕈碱ACh受体降低了它们的繁殖力。因此,簇绒细胞是幼稚小鼠的前哨细胞,并且它们在蠕虫感染时的扩增提供了额外的2型免疫应答效应子功能。