Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, 12203 Berlin, Germany.
Department of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203 Berlin, Germany.
Int J Mol Sci. 2023 Mar 24;24(7):6197. doi: 10.3390/ijms24076197.
() can cause different pathologies, e.g., Whipple's disease and transient gastroenteritis. The mechanism by which the bacteria pass the intestinal epithelial barrier, and the mechanism of -induced gastroenteritis are currently unknown.
Using ex vivo disease models comprising human duodenal mucosa exposed to in Ussing chambers, various intestinal epithelial cell (IEC) cultures exposed to and a macrophage/IEC coculture model served to characterize endocytic uptake mechanisms and barrier function.
exposed ex vivo to human small intestinal mucosae is capable of autonomously entering IECs, thereby invading the mucosa. Using dominant-negative mutants, uptake was shown to be dynamin- and caveolin-dependent but independent of clathrin-mediated endocytosis. Complementary inhibitor experiments suggested a role for the activation of the Ras/Rac1 pathway and actin polymerization. -invaded IECs underwent apoptosis, thereby causing an epithelial barrier defect, and were subsequently subject to phagocytosis by macrophages.
enters epithelia via an actin-, dynamin-, caveolin-, and Ras-Rac1-dependent endocytosis mechanism and consecutively causes IEC apoptosis primarily in IECs invaded by multiple bacteria. This results in a barrier leak. Moreover, we propose that -packed IECs can be subject to phagocytic uptake by macrophages, thereby opening a potential entry point of into intestinal macrophages.
（细菌）可导致不同的病理学变化，例如惠普尔病和一过性肠胃炎。目前尚不清楚细菌如何穿过肠上皮屏障，以及细菌引起肠胃炎的机制。
使用包含暴露于人十二指肠黏膜的离体疾病模型、暴露于的各种肠上皮细胞（IEC）培养物以及巨噬细胞/IEC共培养模型，用于表征细胞内吞摄取机制和屏障功能。
在体外用细菌暴露于人体小肠黏膜，可自主进入 IEC，从而侵犯黏膜。使用显性负突变体表明摄取依赖于胞质动力蛋白和小窝蛋白，但不依赖于网格蛋白介导的内吞作用。互补抑制剂实验表明 Ras/Rac1 途径的激活和肌动蛋白聚合起作用。入侵的 IEC 发生细胞凋亡，从而导致上皮屏障缺陷，随后被巨噬细胞吞噬。
细菌通过肌动蛋白、胞质动力蛋白、小窝蛋白和 Ras/Rac1 依赖的内吞作用机制进入上皮细胞，并随后导致主要被多个细菌入侵的 IEC 发生细胞凋亡。这会导致屏障渗漏。此外，我们提出被细菌包裹的 IEC 可被巨噬细胞吞噬，从而为细菌进入肠道巨噬细胞开辟了一个潜在的入口。
