Cadaverine prevents the escape of Shigella flexneri from the phagolysosome:: A connection between bacterial dissemination and neutrophil transepithelial signaling
Cadaverine prevents the escape of Shigella flexneri from the phagolysosome:: A connection between bacterial dissemination and neutrophil transepithelial signaling
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DOI：
10.1086/323035
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发表时间：
2001-09-15
影响因子：
6.4
通讯作者：
McCormick, BA
中科院分区：
文献类型：
--
作者：
Fernandez, IM;Silva, M;McCormick, BA
福氏志贺菌通过侵袭结肠上皮细胞引起人类细菌性痢疾，其特征是急性富含多形核白细胞(PMNL)的炎症。我们最近的研究表明，卡维林是一种多胺，它能特异性地阻断福氏志贺氏菌诱导的跨上皮信号转导PMNL。在这里，我们深入了解了身体碱减弱志贺氏菌诱导PMNL信号的能力的细胞机制。研究发现，身体碱延缓了含有志贺氏菌的液泡的裂解，这表明建立了一种阻止病原体与细胞骨架充分相互作用的屏障。此外，福氏志贺氏菌ICSA突变体不能与细胞骨架相互作用并传播到细胞间，不能诱导PMNL的移行。结果表明，身体碱诱导的志贺氏菌对吞噬溶酶体的区域化可能是宿主的一种保护性反应，直接导致PMNL跨模型肠上皮迁移的能力减弱。
Shigella flexneri causes bacillary dysentery in humans by invading epithelial cells of the colon, which is characterized by an acute polymorphonuclear leukocyte (PMNL)-rich inflammation. Our recent studies demonstrated that cadaverine, a polyamine, specifically acts to abrogate transepithelial signaling to PMNL induced by S. flexneri. Here, insight is provided into the cellular mechanisms by which cadaverine attenuates the ability of Shigella species to induce PMNL signaling. It was found that cadaverine retards the lysis of the Shigella species-containing vacuole, suggesting that a blockade is established, in which the pathogen is prevented from adequately interacting with the cytoskeleton. Furthermore, an IcsA mutant of S. flexneri that cannot interact with the cytoskeleton and spreads intercellularly fails to induce transmigration of PMNL. Results indicate that cadaverine-induced compartmentalization of Shigella species to the phagolysosome might be a protective response of the host that directly contributes to the diminished ability of PMNL to transmigrate across model intestinal epithelia.