Wine Eytan, Chan Voon L, Sherman Philip M
Department of Paediatrics, University of Toronto, Toronto, Ontario, M5G 1X8, Canada.
Pediatr Res. 2008 Dec;64(6):599-604. doi: 10.1203/PDR.0b013e31818702b9.
The precise mechanism by which the most common cause of bacterial enterocolitis in humans, Campylobacter jejuni, perturbs the intestinal mucosa remains elusive. To define effects of C. jejuni infection on mucosal permeability, Madin-Darby canine kidney (MDCK)-I and T84 cell monolayers were infected with C. jejuni for up to 48 h. All three tested C. jejuni strains caused a 73-78% reduction in transepithelial electrical resistance (TER) in intestinal (T84) cell monolayers, whereas only one strain slightly reduced TER of MDCK-I cells by 25% after 48 h infection. Infection with C. jejuni strains also caused a 2.3-4.5-fold increase in dextran permeability, but only in T84 cells. C. jejuni infection of monolayers also caused morphologic changes in desmosomes, observed by transmission electron microscopy. The cell-type specificity, demonstrated by increased T84 monolayer permeability, correlated with higher bacterial invasion into these cells, relative to MDCK-I cells. In T84 cells, invasion and bacterial translocation preceded barrier disruption and inhibition of C. jejuni invasion using a pharmacological inhibitor of phosphoinositide 3-kinase, reduced the drop in TER. These findings suggest that C. jejuni disruption of monolayers is mediated by invasion, provide new insights into C. jejuni-host epithelial barrier interactions, and offer potential mechanisms of intestinal injury and chronic immune stimulation.
人类细菌性小肠结肠炎最常见的病因——空肠弯曲菌扰乱肠黏膜的确切机制仍不清楚。为了确定空肠弯曲菌感染对黏膜通透性的影响，将空肠弯曲菌感染麦迪逊-达比犬肾（MDCK）-I细胞单层和T84细胞单层长达48小时。所测试的三种空肠弯曲菌菌株均使肠道（T84）细胞单层的跨上皮电阻（TER）降低了73%-78%，而在感染48小时后，只有一种菌株使MDCK-I细胞的TER略有降低，降幅为25%。空肠弯曲菌菌株感染还使右旋糖酐通透性增加了2.3-4.5倍，但仅在T84细胞中出现这种情况。通过透射电子显微镜观察发现，空肠弯曲菌感染细胞单层还会引起桥粒的形态变化。T84细胞单层通透性增加所显示的细胞类型特异性，与相对于MDCK-I细胞而言，这些细胞中更高的细菌侵袭率相关。在T84细胞中，侵袭和细菌易位先于屏障破坏，使用磷酸肌醇3-激酶的药理抑制剂抑制空肠弯曲菌的侵袭，可减少TER的下降。这些发现表明，空肠弯曲菌对细胞单层的破坏是由侵袭介导的，为空肠弯曲菌与宿主上皮屏障的相互作用提供了新的见解，并为肠道损伤和慢性免疫刺激提供了潜在机制。
