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钩端螺旋体穿越极化的肾近端小管上皮细胞时顶端连接复合体的解体。

Disassembly of the apical junctional complex during the transmigration of Leptospira interrogans across polarized renal proximal tubule epithelial cells.

机构信息

Department of Bacteriology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

出版信息

Cell Microbiol. 2021 Sep;23(9):e13343. doi: 10.1111/cmi.13343. Epub 2021 May 6.

DOI:10.1111/cmi.13343
PMID:33864347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8459228/
Abstract

Bacterial pathogens have evolved multiple strategies to disassemble epithelial cell apical junctional complexes (AJCs) and infect epithelial cells. Leptospirosis is a widespread zoonotic infection, mainly caused by Leptospira interrogans, and its dissemination across host cell barriers is essential for its pathogenesis. However, the mechanism of bacterial dissemination across epithelial cell barriers remains poorly characterised. In this study, we analysed the interaction of L. interrogans with renal proximal tubule epithelial cells (RPTECs) and found that at 24 hr post-infection, L. interrogans remain in close contact with the plasma membrane of the RPTEC by extracellularly adhering or crawling. Leptospira interrogans cleaved E-cadherin and induced its endocytosis with release of the soluble N-terminal fragment into the extracellular medium. Concomitantly, a gradual decrease in transepithelial electrical resistance (TEER), mislocalisation of AJC proteins (occludin, claudin-10, ZO-1, and cingulin) and cytoskeletal rearrangement were observed. Inhibition of clathrin-mediated E-cadherin endocytosis prevented the decrease in TEER. We showed that disassembly of AJCs in epithelial cells and transmigration of bacteria through the paracellular route are important for the dissemination of L. interrogans in the host.

摘要

细菌病原体进化出多种策略来分解上皮细胞顶端连接复合体（AJC）并感染上皮细胞。钩端螺旋体病是一种广泛流行的人畜共患病，主要由问号钩端螺旋体引起，其在宿主细胞屏障中的传播对于其发病机制至关重要。然而，细菌在穿过上皮细胞屏障的传播机制仍未得到充分描述。在这项研究中，我们分析了问号钩端螺旋体与肾近端小管上皮细胞（RPTEC）的相互作用，发现感染 24 小时后，问号钩端螺旋体通过细胞外黏附和爬行与 RPTEC 的质膜保持紧密接触。问号钩端螺旋体切割 E-钙黏蛋白并诱导其内化，将可溶性 N 端片段释放到细胞外介质中。同时，观察到跨上皮电阻（TEER）逐渐降低，AJC 蛋白（occludin、claudin-10、ZO-1 和 cingulin）定位异常和细胞骨架重排。网格蛋白介导的 E-钙黏蛋白内吞作用的抑制阻止了 TEER 的降低。我们表明，上皮细胞中 AJC 的解体和细菌通过细胞旁途径的迁移对于问号钩端螺旋体在宿主中的传播很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/5eb1a5dcae8a/CMI-23-e13343-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/e56f89b6c03f/CMI-23-e13343-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/cbc0bcff9f65/CMI-23-e13343-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/d9c65a2d2120/CMI-23-e13343-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/bb8703036224/CMI-23-e13343-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/cb8c2e28d927/CMI-23-e13343-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/aa38f1e94455/CMI-23-e13343-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/2c2cb83ea560/CMI-23-e13343-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/5eb1a5dcae8a/CMI-23-e13343-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/e56f89b6c03f/CMI-23-e13343-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/cbc0bcff9f65/CMI-23-e13343-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/d9c65a2d2120/CMI-23-e13343-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/bb8703036224/CMI-23-e13343-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/cb8c2e28d927/CMI-23-e13343-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/aa38f1e94455/CMI-23-e13343-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/2c2cb83ea560/CMI-23-e13343-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/8459228/5eb1a5dcae8a/CMI-23-e13343-g005.jpg

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