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

Drurey, C. et al. (2022) Intestinal epithelial tuft cell induction is negated by a murine helminth and its secreted products. Journal of Experimental Medicine, 219(1), e20211140. (doi: 10.1084/jem.20211140) (PMID:34779829) (PMCID:PMC8597987)

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Abstract

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.

Item Type:Articles
Additional Information:This work was supported by the Wellcome Trust through an Investigator Award to RMM (Ref 1219530), a Collaborative Grant (Ref 211814) and the Wellcome Trust core-funded Wellcome Centre for Integrative Parasitology (Ref: 104111).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Campillo Poveda, Dr Marta and Coakley, Miss Gillian and Drurey, Claire and Maizels, Professor Rick
Authors: Drurey, C., Lindholm, H. T., Coakley, G., Campillo Poveda, M., Löser, S., Doolan, R., Gerbe, F., Jay, P., Harris, N., Oudhoff, M. J., and Maizels, R. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN:0022-1007
ISSN (Online):1540-9538
Published Online:15 November 2021
Copyright Holders:Copyright © 2021 Drurey et al.
First Published:First published in Journal of Experimental Medicine 219(1): e20211140
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZIII - Parasitology
302416Tuft cells, sensors adn effectors in immunity to helminthsRichard MaizelsWellcome Trust (WELLCOTR)211814/Z/18/ZIII - Parasitology
308411Molecular and Cellular Interactions in Helminth InfectionsRichard MaizelsWellcome Trust (WELLCOTR)219530/Z/19/ZIII - Parasitology