%0 Journal Article
%T Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity.
%A Ndjim M
%A Gasmi I
%A Herbert F
%A Joséphine C
%A Bas J
%A Lamrani A
%A Coutry N
%A Henry S
%A Zimmermann VS
%A Dardalhon V
%A Campillo Poveda M
%A Turtoi E
%A Thirard S
%A Forichon L
%A Giordano A
%A Ciancia C
%A Homayed Z
%A Pannequin J
%A Britton C
%A Devaney E
%A McNeilly TN
%A Berrard S
%A Turtoi A
%A Maizels RM
%A Gerbe F
%A Jay P
%J Immunity
%V 57
%N 6
%D 2024 Jun 11
%M 38744292
%F 43.474
%R 10.1016/j.immuni.2024.04.018
%X 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.