Evidence that tight junctions are disrupted due to intimate bacterial contact and not inflammation during attaching and effacing pathogen infection in vivo
Evidence that tight junctions are disrupted due to intimate bacterial contact and not inflammation during attaching and effacing pathogen infection in vivo
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DOI：
10.1128/iai.00721-06
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发表时间：
2006-11-01
影响因子：
3.1
通讯作者：
Finlay, B. Brett
中科院分区：
文献类型：
--
作者：
Guttman, Julian A.;Samji, Fereshte N.;Finlay, B. Brett
人们普遍认为，紧密连接在感染过程中通过附着和消除（A/E）病原体而改变。这些破坏已经在体外和最近在体内证明。对于体内实验，用啮齿柠檬酸杆菌A/E感染的鼠模型是选择的动物模型。除了对紧密连接的影响外，这些细菌还以高水平定殖结肠，消除结肠细胞微绒毛，并引起增生和炎症。虽然我们最近已经证明，紧密连接被破坏的啮齿类C，与炎症的间接影响的上皮细胞连接的细菌的直接影响的问题仍然有待澄清。在这里，我们证明，在C。在啮齿类感染中，炎症在紧密连接的改变中没有明显的作用。紧密连接蛋白claudin-1、claudin-3和claudin-5的分布在发炎的结肠中不受影响，并且当通过电子显微镜观察时，连接在形态上没有改变。此外，示踪分子不能穿透已清除细菌的感染小鼠的发炎结肠上皮。最后，从暴露于C.具有高水平的细菌附着于结肠细胞以及炎症的啮齿动物14天，具有特征性的改变的紧密连接蛋白定位，而与感染的结肠细胞相邻的细胞保持其正常的紧密连接蛋白分布。我们的结论是炎症在A/E发病过程中的紧密连接改变中没有明显的作用，体内紧密连接破坏似乎只依赖于致病菌与细胞的直接紧密附着。
It is widely accepted that tight junctions are altered during infections by attaching and effacing (A/E) pathogens. These disruptions have been demonstrated both in vitro and more recently in vivo. For in vivo experiments, the murine model of A/E infection with Citrobacter rodentium is the animal model of choice. In addition to effects on tight junctions, these bacteria also colonize the colon at high levels, efface colonocyte microvilli, and cause hyperplasia and inflammation. Although we have recently demonstrated that tight junctions are disrupted by C rodentium, the issue of direct effects of bacteria on epithelial cell junctions versus the indirect effects of inflammation still remains to be clarified. Here, we demonstrate that during the C. rodentium infections, inflammation plays no discernible role in the alteration of tight junctions. The distribution of the tight junction proteins, claudin-1, -3, and -5, are unaffected in inflamed colon, and junctions appear morphologically unaltered when viewed by electron microscopy. Additionally, tracer molecules are not capable of penetrating the inflamed colonic epithelium of infected mice that have cleared the bacteria. Finally, infected colonocytes from mice exposed to C. rodentium for 14 days, which have high levels of bacterial attachment to colonocytes as well as inflammation, have characteristic, altered claudin localization whereas cells adjacent to infected colonocytes retain their normal claudin distribution. We conclude that inflammation plays no discernible role in tight junction alteration during A/E pathogenesis and that tight junction disruption in vivo appears dependent only on the direct intimate attachment of the pathogenic bacteria to the cells.