Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity - UNICANCER Access content directly
Journal Articles Immunity Year : 2024

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

Nathalie Coutry
Sylvain Henry
  • Function : Author
Evgenia Turtoi
  • Function : Author
Julie Pannequin

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.
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hal-04576461 , version 1 (19-06-2024)

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Marième Ndjim, Imène Gasmi, Fabien Herbert, Charlène Joséphine, Julie Bas, et al.. Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity. Immunity, 2024, 57 (6), pp.1260-1273.e7. ⟨10.1016/j.immuni.2024.04.018⟩. ⟨hal-04576461⟩
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