Li Diyin, Yang Qi, Luo Jianhua, Xu Yangyushuang, Li Jingqing, Tao Liang
College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Research Center for Industries of the Future and Key Laboratory of Multi-omics in Infection and Immunity of Zhejiang Province, School of Medicine, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Cell Discov. 2024 Nov 5;10(1):112. doi: 10.1038/s41421-024-00729-1.
Migracytosis is a recently described cellular process that generates and releases membrane-bound pomegranate-like organelles called migrasomes. Migracytosis normally occurs during cell migration, participating in various intercellular biological functions. Here, we report a new type of migracytosis induced by small GTPase-targeting toxins. Unlike classic migracytosis, toxin-induced migrasome formation does not rely on cell migration and thus can occur in both mobile and immobile cells. Such non-canonical migracytosis allows the cells to promptly respond to microbial stimuli such as bacterial toxins and effectors and release informative cellular contents in bulk. We demonstrated that C. difficile TcdB3 induces liver endothelial cells and Kupffer cells to produce migrasomes in vivo. Moreover, the migracytosis-defective Tspan9 mice show less acute inflammation and lower lethality rate in the toxin challenge assay. Therefore, we propose that the non-canonical migracytosis acts as a new mechanism for mammalian species to sense and exacerbate early immune response upon microbial infections.
迁移小体形成是一种最近被描述的细胞过程，它产生并释放被称为迁移小体的膜结合石榴样细胞器。迁移小体形成通常发生在细胞迁移过程中，参与各种细胞间生物学功能。在此，我们报道了一种由靶向小GTP酶的毒素诱导的新型迁移小体形成。与经典的迁移小体形成不同，毒素诱导的迁移小体形成不依赖于细胞迁移，因此可以在移动和静止细胞中发生。这种非经典的迁移小体形成使细胞能够迅速响应微生物刺激，如细菌毒素和效应蛋白，并大量释放信息性细胞内容物。我们证明艰难梭菌TcdB3在体内诱导肝内皮细胞和库普弗细胞产生迁移小体。此外，迁移小体形成缺陷的Tspan9小鼠在毒素攻击试验中表现出较轻的急性炎症和较低的致死率。因此，我们提出非经典的迁移小体形成作为一种新机制，使哺乳动物在微生物感染时感知并加剧早期免疫反应。
