Fernandez I M, Silva M, Schuch R, Walker W A, Siber A M, Maurelli A T, McCormick B A
Mucosal Immunology Laboratories, Department of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Charlestown, Massachusetts 02129-4404, USA.
J Infect Dis. 2001 Sep 15;184(6):743-53. doi: 10.1086/323035. Epub 2001 Aug 24.
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.
福氏志贺菌通过侵入结肠上皮细胞导致人类患细菌性痢疾，其特征是急性多形核白细胞（PMNL）丰富的炎症。我们最近的研究表明，腐胺这种多胺可特异性地消除福氏志贺菌诱导的向PMNL的跨上皮信号传导。本文深入探讨了腐胺减弱志贺菌属诱导PMNL信号传导能力的细胞机制。研究发现，腐胺会延迟含志贺菌属液泡的裂解，这表明形成了一种阻断，使病原体无法与细胞骨架充分相互作用。此外，无法与细胞骨架相互作用且不能在细胞间扩散的福氏志贺菌IcsA突变体无法诱导PMNL的迁移。结果表明，腐胺诱导志贺菌属定位于吞噬溶酶体可能是宿主的一种保护反应，直接导致PMNL穿越模型肠上皮细胞迁移的能力减弱。
