麦吉尔大学健康中心研究所Irah L. King研究组取得一项新突破。他们报道了1型免疫基质细胞网络介导对肠道感染的疾病耐受。相关论文于2025年4月22日发表在《细胞》杂志上。
课题组研究人员证明了快速诱导干扰素γ (IFNγ)信号协调多细胞反应，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感测也限制了表达平滑肌动蛋白的细胞的扩张，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。他们的研究结果对处理感染后肠道功能障碍和与基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。
据悉，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。
附：英文原文
Title: A type 1 immune-stromal cell network mediates disease tolerance against intestinal infection
Author: Susan Westfall, Maria E. Gentile, Tayla M. Olsen, Danielle Karo-Atar, Andrei Bogza, Franziska Rstel, 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
Issue&Volume: 2025-04-22
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.
DOI: 10.1016/j.cell.2025.03.043
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00395-2