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Article Dans Une Revue Journal of Experimental Medicine Année : 2022

Intestinal epithelial tuft cell induction is negated by a murine helminth and its secreted products

Claire Drurey
Håvard T Lindholm
Gillian Coakley
Marta Campillo Poveda
Stephan Löser
Rory Doolan
François Gerbe
Philippe Jay
Nicola Harris
Menno J Oudhoff
Rick M Maizels

Résumé

Helminth parasites are adept manipulators of the immune system, using multiple strategies to evade the host type 2 response. In the intestinal niche, the epithelium is crucial for initiating type 2 immunity via tuft cells, which together with goblet cells expand dramatically in response to the type 2 cytokines IL-4 and IL-13. However, it is not known whether helminths modulate these epithelial cell populations. In vitro, using small intestinal organoids, we found that excretory/secretory products (HpES) from Heligmosomoides polygyrus blocked the effects of IL-4/13, inhibiting tuft and goblet cell gene expression and expansion, and inducing spheroid growth characteristic of fetal epithelium and homeostatic repair. Similar outcomes were seen in organoids exposed to parasite larvae. In vivo, H. polygyrus infection inhibited tuft cell responses to heterologous Nippostrongylus brasiliensis infection or succinate, and HpES also reduced succinate-stimulated tuft cell expansion. Our results demonstrate that helminth parasites reshape their intestinal environment in a novel strategy for undermining the host protective response.
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Dates et versions

hal-03850320 , version 1 (13-11-2022)

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Claire Drurey, Håvard T Lindholm, Gillian Coakley, Marta Campillo Poveda, Stephan Löser, et al.. Intestinal epithelial tuft cell induction is negated by a murine helminth and its secreted products. Journal of Experimental Medicine, 2022, 219 (1), ⟨10.1084/jem.20211140⟩. ⟨hal-03850320⟩
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