Preprint:

A type 1 immune-stromal cell network mediates disease tolerance and barrier protection against intestinal infection.

Westfall S, Gentile ME, Olsen TM, Karo-Atar D, Bogza A, Röstel F, Pardy RD, Mandato G, Fontes G, View ORCID Profile De’Broski H, Melichar HJ, Abadie V, Richer MJ, Vinh DC, Koenig JFE, View ORCID Profile Harrison OJ, View ORCID Profile Divangahi M, Weis S, Gregorieff A, View ORCID Profile King IL (2024) A type 1 immune-stromal cell network mediates disease tolerance and barrier protection against intestinal infection. bioRxiv [Preprint]

Abstract

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 IFNγ signaling coordinates a multi-cellular 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 had limited impact on 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 remodelling.

Leibniz-HKI-Authors

Franziska Röstel
Sebastian Weis

Identifier

doi: 10.1101/2024.09.04.611190