A type 1 immune-stromal cell network mediates disease tolerance against intestinal infection

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2025-04-22 DOI:10.1016/j.cell.2025.03.043

Susan Westfall, Maria E. Gentile, Tayla M. Olsen, Danielle Karo-Atar, Andrei Bogza, Franziska Röstel, Ryan D. Pardy, Giordano Mandato, Ghislaine Fontes, De’Broski Herbert, Heather J. Melichar, Valerie Abadie, Martin J. Richer, Donald C. Vinh, Joshua F.E. Koenig, Oliver J. Harrison, Maziar Divangahi, Sebastian Weis, Alex Gregorieff, Irah L. King

{"title":"A type 1 immune-stromal cell network mediates disease tolerance against intestinal infection","authors":"Susan Westfall, Maria E. Gentile, Tayla M. Olsen, Danielle Karo-Atar, Andrei Bogza, Franziska Röstel, Ryan D. Pardy, Giordano Mandato, Ghislaine Fontes, De’Broski Herbert, Heather J. Melichar, Valerie Abadie, Martin J. Richer, Donald C. Vinh, Joshua F.E. Koenig, Oliver J. Harrison, Maziar Divangahi, Sebastian Weis, Alex Gregorieff, Irah L. King","doi":"10.1016/j.cell.2025.03.043","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 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<sup>+</sup> 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.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"7 1","pages":""},"PeriodicalIF":45.5000,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2025.03.043","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

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 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.

Abstract Image

查看原文本刊更多论文

1型免疫基质细胞网络介导对肠道感染的疾病耐受

1型免疫通过消除病原体介导宿主防御，但这一途径是否也影响组织功能尚不清楚。在这里，我们证明了干扰素γ (IFNγ)信号的快速诱导协调了多细胞反应，这对于限制组织损伤和维持组织侵入性蠕虫感染小鼠后的肠道运动至关重要。IFNγ的产生是由固有层CD8+ T细胞在寄生虫诱导的屏障入侵过程中myd88依赖的微生物群识别后的抗原非依赖性激活启动的。IFNγ直接作用于肠基质细胞募集中性粒细胞，从而限制寄生虫诱导的组织损伤。IFNγ感测也限制了平滑肌肌动蛋白表达细胞的扩张，以防止病理性肠道运动障碍。重要的是，这种组织保护反应不影响寄生虫负担，表明IFNγ支持疾病耐受性防御策略。我们的研究结果对处理感染后肠道功能障碍和与间质重塑相关的慢性炎症性疾病的病理生理后遗症具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.