Bacterial toxins induce non-canonical migracytosis to aggravate acute inflammation.

IF 13 1区 生物学 Q1 CELL BIOLOGY Cell Discovery Pub Date : 2024-11-05 DOI:10.1038/s41421-024-00729-1
Diyin Li, Qi Yang, Jianhua Luo, Yangyushuang Xu, Jingqing Li, Liang Tao
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Abstract

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.

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细菌毒素会诱发非典型移行细胞增多症,从而加重急性炎症。
移行体(Migracytosis)是最近描述的一种细胞过程,它生成并释放膜结合的石榴状细胞器,称为移行体。移行体通常发生在细胞迁移过程中,参与各种细胞间生物功能。在这里,我们报告了一种由小 GTP 酶靶向毒素诱导的新型移行体。与传统的移行作用不同,毒素诱导的移行体形成并不依赖于细胞迁移,因此既可发生在移动的细胞中,也可发生在不移动的细胞中。这种非典型的移行作用使细胞能够对细菌毒素和效应物等微生物刺激做出迅速反应,并大量释放信息丰富的细胞内容物。我们证实,艰难梭菌 TcdB3 能诱导肝脏内皮细胞和 Kupffer 细胞在体内产生移行体。此外,在毒素挑战实验中,移行体缺陷的 Tspan9-/- 小鼠表现出较少的急性炎症和较低的致死率。因此,我们认为非典型的移行体是哺乳动物感知微生物感染并加剧早期免疫反应的一种新机制。
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来源期刊
Cell Discovery
Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍: Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.
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