Specific entry of Helicobacter pylori into cultured gastric epithelial cells via a zipper-like mechanism
Specific entry of Helicobacter pylori into cultured gastric epithelial cells via a zipper-like mechanism
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DOI：
10.1128/iai.70.4.2108-2120.2002
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发表时间：
2002-04-01
影响因子：
3.1
通讯作者：
Meyer, TF
中科院分区：
文献类型：
--
作者：
Kwok, T;Backert, S;Meyer, TF
虽然幽门螺杆菌通常被认为是一种细胞外病原体，但许多体外感染实验和活检检查表明，它偶尔能够进入哺乳动物宿主细胞。在这里，我们通过使用AGS细胞作为宿主细胞模型来表征这种进入过程。在庆大霉素保护-侵袭试验中，H。pylori菌落的回收率低于25 ℃下生长的沙门氏菌血清型鼠伤寒X22、表达InvA的大肠杆菌和小肠结肠炎耶尔森氏菌YO：9，但高于淋病奈瑟氏菌VP 1和Y。小肠结肠炎菌YO：9在37 ℃下生长。在超微结构水平上，观察到进入过程通过拉链样机制发生。内化H. pylori结合在紧密的含LAMP-1的空泡中，与浓缩的丝状肌动蛋白和酪氨酸磷酸化信号密切相关。Wortmannin，一种有效的磷脂酰肌醇3-激酶抑制剂，和calphostin C，一种蛋白激酶C抑制剂，都能抑制H。幽门螺杆菌的敏感性和剂量依赖性的方式;然而，钒酸钠，酪氨酸磷酸酶和ATP酶的抑制剂，增强了进入的水平。此外，细胞因子肿瘤坏死因子α拮抗H。pylori进入AGS细胞。总的来说，这些结果表明。进入H。幽门螺杆菌进入AGS细胞的过程是通过拉链样机制发生的，该机制涉及各种宿主信号转导事件。
Although Helicobacter pylori has generally been considered an extracellular pathogen, a number of in vitro infection experiments and biopsy examinations have shown that it is capable of occasionally entering mammalian host cells. Here, we characterized this entry process by using AGS cells as a host cell model. In gentamicin protection-invasion assays, the number of H. pylori colonies recovered was lower than that for Salmonella enterica serovar Typhimurium X22, Escherichia coli expressing InvA, and Yersinia enterocolitica YO:9 grown at 25degreesC but higher than that for Neisseria gonorrhoeae VP1 and Y. enterocolitica YO:9 grown at 37degreesC. At the ultrastructural level, the entry process was observed to occur via a zipper-like mechanism. Internalized H. pylori was bound in tight LAMP-1-containing vacuoles in close association with condensed filamentous actin and tyrosine phosphorylation signals. Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, and calphostin C, an inhibitor of protein kinase C, both inhibited the entry of H. pylori in a sensitive and dose-dependent manner; however, the level of entry was enhanced by sodium vanadate, an inhibitor of tyrosine phosphatases and ATPases. Furthermore, the cytokine tumor necrosis factor alpha antagonized the entry of H. pylori into AGS cells. Collectively, these results demonstrate that the. entry of H. pylori into AGS cells occurs via a zipper-like mechanism which involves various host signal transduction events.