Susan Westfall, Maria E Gentile, Tayla M Olsen, Danielle Karo-Atar, Andrei Bogza, Franziska Roestel, Ryan Pardy, Giordano Mandato, Ghislaine Fontes, DeBroski Herbert, Heather J Melichar, Valerie Abadie, Martin Richer, Donald C Vinh, Joshua FE Koenig, Oliver J Harrison, Maziar J Divangahi, Sebastian Weis, Alex Gregorieff, Irah L King
{"title":"1 型免疫间质细胞网络介导疾病耐受和肠道感染屏障保护","authors":"Susan Westfall, Maria E Gentile, Tayla M Olsen, Danielle Karo-Atar, Andrei Bogza, Franziska Roestel, Ryan Pardy, Giordano Mandato, Ghislaine Fontes, DeBroski Herbert, Heather J Melichar, Valerie Abadie, Martin Richer, Donald C Vinh, Joshua FE Koenig, Oliver J Harrison, Maziar J Divangahi, Sebastian Weis, Alex Gregorieff, Irah L King","doi":"10.1101/2024.09.04.611190","DOIUrl":null,"url":null,"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 IFNg 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. IFNg 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. IFNg acted directly on intestinal stromal cells to recruit neutrophils that limited parasite-induced tissue injury. IFNg 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 IFNg 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.","PeriodicalId":501182,"journal":{"name":"bioRxiv - Immunology","volume":"20 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A type 1 immune-stromal cell network mediates disease tolerance and barrier protection against intestinal infection\",\"authors\":\"Susan Westfall, Maria E Gentile, Tayla M Olsen, Danielle Karo-Atar, Andrei Bogza, Franziska Roestel, Ryan Pardy, Giordano Mandato, Ghislaine Fontes, DeBroski Herbert, Heather J Melichar, Valerie Abadie, Martin Richer, Donald C Vinh, Joshua FE Koenig, Oliver J Harrison, Maziar J Divangahi, Sebastian Weis, Alex Gregorieff, Irah L King\",\"doi\":\"10.1101/2024.09.04.611190\",\"DOIUrl\":null,\"url\":null,\"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 IFNg 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. IFNg 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. IFNg acted directly on intestinal stromal cells to recruit neutrophils that limited parasite-induced tissue injury. IFNg 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 IFNg 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.\",\"PeriodicalId\":501182,\"journal\":{\"name\":\"bioRxiv - Immunology\",\"volume\":\"20 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv - Immunology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.09.04.611190\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.09.04.611190","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
A type 1 immune-stromal cell network mediates disease tolerance and barrier protection against intestinal infection
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 IFNg 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. IFNg 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. IFNg acted directly on intestinal stromal cells to recruit neutrophils that limited parasite-induced tissue injury. IFNg 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 IFNg 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.