Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity

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Ndjim, Marième | Gasmi, Imène | Herbert, Fabien | Joséphine, Charlène | Bas, Julie | Lamrani, Ali | Coutry, Nathalie | Henry, Sylvain | Zimmermann, Valérie | Dardalhon, Valérie | Campillo Poveda, Marta | Turtoi, Evgenia | Thirard, Steeve | Forichon, Luc | Giordano, Alicia | Ciancia, Claire | Homayed, Zeinab | Pannequin, Julie | Britton, Collette | Devaney, Eileen | Mcneilly, Tom | Berrard, Sylvie | Turtoi, Andrei | Maizels, Rick | Gerbe, François | Jay, Philippe

Edité par CCSD ; Elsevier -

International audience. 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.

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