Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity
Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity
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DOI：
10.1086/386289
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发表时间：
2004-05-15
影响因子：
6.4
通讯作者：
Peek, RM
中科院分区：
文献类型：
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作者：
Gewirtz, AT;Yu, YM;Peek, RM
除非用药物根除幽门螺杆菌，否则幽门螺杆菌会在人的胃里定居数十年。我们推测，这种鞭毛病原体逃避免疫清除，部分是通过避免被鞭毛受体Toll样受体5(TLR5)检测到的。与其他革兰氏阴性菌不同，幽门螺杆菌不释放鞭毛。此外，重组幽门螺杆菌鞭毛蛋白(FLAA)刺激TLR5介导的IL-8分泌的能力明显低于鼠伤寒沙门氏菌鞭毛蛋白(1000倍)。TLR5可通过p38丝裂原活化蛋白激酶信号转导鞭毛蛋白诱导的IL-8分泌；然而，与鼠伤寒沙门氏菌鞭毛蛋白的诱导作用相比，幽门螺杆菌依赖于FlaA的p38激活作用明显减弱。此外，幽门螺杆菌FlaA基因的破坏降低了幽门螺杆菌的运动能力，但对幽门螺杆菌诱导的IL-8的分泌无影响，表明幽门螺杆菌鞭毛蛋白在激活炎症上皮细胞的协调中没有作用。我们得出结论，幽门螺杆菌逃避TLR5介导的检测，这可能是其在单个宿主中长期存在的原因。
Helicobacter pylori colonizes the human stomach for decades unless pharmacologically eradicated. We hypothesized that this flagellated pathogen escapes immune clearance, in part, by avoiding detection by the flagellin receptor Toll-like receptor 5 (TLR5). In contrast to other gram-negative microbes, H. pylori did not release flagellin. Furthermore, recombinant H. pylori flagellin (FlaA) was significantly less potent (1000-fold) than Salmonella typhimurium flagellin in activating TLR5-mediated interleukin (IL)-8 secretion. TLR5 can mediate flagellin-induced IL-8 secretion via p38 mitogen-activated protein kinase signaling; however, compared with potent induction by S. typhimurium flagellin, H. pylori FlaA-dependent p38 activation was substantially attenuated. In addition, disruption of H. pylori flaA decreased motility but had no effect on H. pylori - induced IL-8 secretion, which indicates that H. pylori flagellin plays no role in activating epithelial orchestration of inflammation. We conclude that H. pylori evades TLR5-mediated detection, which may contribute to its long-term persistence in individual hosts.