1. Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity.
- Author
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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, and Jay P
- Subjects
- Animals, Mice, Choline O-Acetyltransferase metabolism, Interleukin-13 metabolism, Interleukin-13 immunology, Mice, Knockout, Mice, Inbred C57BL, Helminthiasis immunology, Helminthiasis parasitology, Epithelial Cells immunology, Epithelial Cells metabolism, Immunity, Innate, Nematospiroides dubius immunology, Tuft Cells, Acetylcholine metabolism, Intestinal Mucosa immunology, Intestinal Mucosa metabolism, Intestinal Mucosa parasitology
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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