Institute of Functional Genomics (IGF), University of Montpellier, CNRS, Inserm, Montpellier, France.
Montpellier Alliance for Metabolomics and Metabolism Analysis, Platform for Translational Oncometabolomics (PLATON), Biocampus, CNRS, INSERM, Université de Montpellier, Montpellier, France.
Immunity. 2024 Jun 11;57(6):1260-1273.e7. doi: 10.1016/j.immuni.2024.04.018. Epub 2024 May 13.
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.
在寄生虫蠕虫感染时，活化的肠类锥体细胞分泌白细胞介素 25（IL-25），启动 2 型免疫应答，固有淋巴样细胞 2 型（ILC2）在其中产生白细胞介素 13。这导致上皮细胞重塑，包括类锥体细胞增生，其功能未知。我们鉴定出类锥体细胞具有胆碱能效应功能，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，上皮细胞特异性 ChAT 缺失的小鼠蠕虫负荷、适应性和粪便卵计数增加，尽管 2 型免疫应答相当。从机制上讲，IL-13 扩增的类锥体细胞将乙酰胆碱（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型乙酰胆碱受体降低其生殖力。因此，类锥体细胞是未致敏小鼠的哨兵，它们在蠕虫感染时的扩增提供了另一种 2 型免疫应答效应功能。
