PDF(Pubmed)
Abstract：
Infection with Helicobacter pylori (H. pylori) affects almost half of the world\'s population and is a major cause of stomach cancer. Although immune cells react strongly to this gastric bacterium, H. pylori is still one of the rare pathogens that can evade elimination by the host and cause chronic inflammation. In the present study, we characterized the inflammatory response of primary human monocytes to repeated H. pylori infection and their responsiveness to an ensuing bacterial stimulus. We show that, although repeated stimulations with H. pylori do not result in an enhanced response, H. pylori-primed monocytes are hyper-responsive to an Escherichia coli-lipopolysaccharide (LPS) stimulation that takes place shortly after infection. This hyper-responsiveness to bacterial stimuli is observed upon infection with viable H. pylori only, while heat-killed H. pylori fails to boost both cytokine secretion and STAT activation in response to LPS. When the secondary challenge occurs several days after the primary infection with live bacteria, H. pylori-infected monocytes lose their hyper-responsiveness. The observation that H. pylori makes primary human monocytes more susceptible to subsequent/overlapping stimuli provides an important basis to better understand how H. pylori can maintain chronic inflammation and thus contribute to gastric cancer progression.
摘要：
幽门螺杆菌感染（H.幽门螺杆菌）影响了世界上近一半的人口，是胃癌的主要原因。尽管免疫细胞对这种胃细菌反应强烈，H.pylori依然是罕见的能逃避宿主消除并惹起慢性炎症的病原体之一。在本研究中,我们表征了原代人单核细胞对反复幽门螺杆菌感染的炎症反应及其对随后细菌刺激的反应。我们证明,尽管反复刺激幽门螺杆菌不会导致反应增强，幽门螺杆菌引发的单核细胞对感染后不久发生的大肠杆菌-脂多糖(LPS)刺激具有高响应性。这种对细菌刺激的高反应性只在感染有活力的幽门螺杆菌时观察到，而热杀死的幽门螺杆菌不能促进响应LPS的细胞因子分泌和STAT激活。当活细菌初次感染后几天发生二次攻击时，幽门螺杆菌感染的单核细胞失去其高反应性。幽门螺杆菌使原代人单核细胞对后续/重叠刺激更敏感的观察结果为更好地理解幽门螺杆菌如何维持慢性炎症并因此促进胃癌进展提供了重要的基础。
