Gastrointestinal Research Group, Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
PLoS One. 2013 Sep 13;8(9):e73339. doi: 10.1371/journal.pone.0073339. eCollection 2013.
The exact mechanism by which Entamoeba histolytica disrupts the human colonic epithelium and invades the mucosa has yet to be clearly elucidated. E. histolytica produces a diverse array of putative virulent factors such as glycosidase, cysteine proteinases and amebapore that can modulate and/or disrupt epithelial barrier functions. However, it is currently thought that E. histolytica produces numerous other molecules and strategies to disrupt colonic mucosal defenses. In this study, we document a putative mechanism whereby the parasite alters the integrity of human epithelium by expressing a cognate tight junction protein of the host. We detected this protein as "occludin-like" as revealed by immunoblotting and immunoprecipitation studies and visualization by confocal microscopy using antibodies highly specific for human occludin. We propose that E. histolytica occludin-like protein might displace mucosal epithelial occludin-occludin tight junction interactions resulting in epithelial disruption analogous to sub mucosal human dendritic cells sampling luminal contents. These results indicate that E. histolytica occludin is a putative virulent component that can play a role in the pathogenesis of intestinal amebiasis.
溶组织内阿米巴破坏人类结肠上皮并侵袭黏膜的确切机制尚未阐明。溶组织内阿米巴产生多种潜在的毒力因子,如糖苷酶、半胱氨酸蛋白酶和阿米巴孔,这些因子可以调节和/或破坏上皮屏障功能。然而,目前认为溶组织内阿米巴产生许多其他分子和策略来破坏结肠黏膜防御。在这项研究中,我们记录了一种寄生虫通过表达宿主同源紧密连接蛋白来改变人上皮完整性的假定机制。我们通过免疫印迹和免疫沉淀研究以及使用针对人紧密连接蛋白 occludin 的高特异性抗体进行共聚焦显微镜观察检测到这种蛋白为“occludin 样”。我们提出,溶组织内阿米巴 occludin 样蛋白可能取代黏膜上皮 occludin-occludin 紧密连接相互作用,导致上皮破坏,类似于黏膜下人类树突状细胞摄取腔内容物。这些结果表明,溶组织内阿米巴 occludin 是一种潜在的毒力成分,可能在肠阿米巴病的发病机制中发挥作用。