Westfall, Susan; Gentile, Maria E; Olsen, Tayla M; Karo-Atar, Danielle; Bogza, Andrei; Röstel, Franziska; Pardy, Ryan D 
ORCID: https://orcid.org/0000-0002-0024-8888; Mandato, Giordano; Fontes, Ghislaine; Herbert, De'Broski; Melichar, Heather J; Abadie, Valerie; Richer, Martin J; Vinh, Donald C; Koenig, Joshua F E; Harrison, Oliver J; Divangahi, Maziar; Weis, Sebastian; Gregorieff, Alex et King, Irah L
(2025).
A type 1 immune-stromal cell network mediates disease tolerance against intestinal infection
Cell
, vol. 188
, nº 043.
pp. 1-17.
DOI: 10.1016/j.cell.2025.03.043.
Résumé
Type 1 immunity mediates host defense through pathogen elimination, but whether this pathway also impacts tissue function is unknown. Here, we demonstrate that rapid induction of interferon γ (IFNγ) signaling coordinates a multicellular response that is critical to limit tissue damage and maintain gut motility following infection of mice with a tissue-invasive helminth. IFNγ production is initiated by antigen-independent activation of lamina propria CD8(+) T cells following MyD88-dependent recognition of the microbiota during helminth-induced barrier invasion. IFNγ acted directly on intestinal stromal cells to recruit neutrophils that limited parasite-induced tissue injury. IFNγ sensing also limited the expansion of smooth muscle actin-expressing cells to prevent pathological gut dysmotility. Importantly, this tissue-protective response did not impact parasite burden, indicating that IFNγ supports a disease tolerance defense strategy. Our results have important implications for managing the pathophysiological sequelae of post-infectious gut dysfunction and chronic inflammatory diseases associated with stromal remodeling.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | IFNg; disease tolerance; gut motility; helminth; microbiota; stroma; tissue-resident memory cells |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 07 juill. 2025 18:54 |
| Dernière modification: | 07 juill. 2025 18:54 |
| URI: | https://espace.inrs.ca/id/eprint/16495 |
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