1. Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity.
- Author
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Ndjim, Marième, Gasmi, Imène, Herbert, Fabien, Joséphine, Charlène, Bas, Julie, Lamrani, Ali, Coutry, Nathalie, Henry, Sylvain, Zimmermann, Valérie S., Dardalhon, Valérie, Campillo Poveda, Marta, Turtoi, Evgenia, Thirard, Steeve, Forichon, Luc, Giordano, Alicia, Ciancia, Claire, Homayed, Zeinab, Pannequin, Julie, Britton, Collette, and Devaney, Eileen
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FECAL egg count , *ACETYLCHOLINE , *MUSCARINIC receptors , *HELMINTHIASIS , *INNATE lymphoid cells - 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. [Display omitted] • Tuft cells play both sentinel and effector roles in type 2 immune responses • Tuft cell acetylcholine production increases during helminth infections • Tuft cells release acetylcholine into the gut lumen during type 2 immune responses • Acetylcloline inhibits helminth fecundity through worm muscarinic receptors Intestinal tuft cells are known as sentinels capable of initiating type 2 immune responses upon parasite infections. Ndjim et al. now report a direct effector function for intestinal tuft cells during such immune responses by increasing their acetylcholine biosynthesis and releasing it into the gut lumen. Helminth fecundity is directly inhibited by acetylcholine, acting through worm muscarinic receptors. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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