{Reference Type}: Journal Article
{Title}: Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity.
{Author}: Ndjim M;Gasmi I;Herbert F;Joséphine C;Bas J;Lamrani A;Coutry N;Henry S;Zimmermann VS;Dardalhon V;Campillo Poveda M;Turtoi E;Thirard S;Forichon L;Giordano A;Ciancia C;Homayed Z;Pannequin J;Britton C;Devaney E;McNeilly TN;Berrard S;Turtoi A;Maizels RM;Gerbe F;Jay P;
{Journal}: Immunity
{Volume}: 57
{Issue}: 6
{Year}: 2024 Jun 11
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2024.04.018
{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.