Kao John Y, Rathinavelu Sivaprakash, Eaton Kathryn A, Bai Longchuan, Zavros Yana, Takami Mimi, Pierzchala Anna, Merchant Juanita L
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109-0682, USA.
Am J Physiol Gastrointest Liver Physiol. 2006 Jul;291(1):G73-81. doi: 10.1152/ajpgi.00139.2005. Epub 2006 Feb 9.
Helicobacter pylori evades host immune defenses and causes chronic gastritis. Immunity against intestinal pathogens is largely mediated by dendritic cells, yet the role of dendritic cells in acute H. pylori infection is largely unknown. We observed the recruitment of dendritic cells to the gastric mucosa of H. pylori-infected mice. Bone marrow-derived dendritic cells from mice responded to live H. pylori by upregulating the expression of proinflammatory cytokine mRNA (i.e., IL-1alpha, IL-1beta, and IL-6). The supernatant from dendritic cells stimulated with H. pylori for 18 h contained twofold higher levels of IL-12p70 than IL-10 and induced the proliferation of syngeneic splenocytes and type 1 T helper cell cytokine release (IFN-gamma and TNF-alpha). These responses were significantly lower compared with those induced by Acinetobacter lwoffi, another gastritis-causing pathogen more susceptible to host defenses. Analysis of whole H. pylori sonicate revealed the presence of a heat-stable factor secreted from H. pylori that specifically inhibited IL-12 but not IL-10 release from dendritic cells activated by A. lwoffi. Our findings suggest that dendritic cells participate in the host immune response against H. pylori and that their suppression by H. pylori may explain why infected hosts fail to prevent bacterial colonization.
幽门螺杆菌可逃避宿主免疫防御并引发慢性胃炎。对肠道病原体的免疫在很大程度上由树突状细胞介导，然而树突状细胞在急性幽门螺杆菌感染中的作用却 largely unknown。我们观察到树突状细胞被招募至幽门螺杆菌感染小鼠的胃黏膜。来自小鼠的骨髓源性树突状细胞通过上调促炎细胞因子mRNA（即白细胞介素-1α、白细胞介素-1β和白细胞介素-6）的表达来对活的幽门螺杆菌作出反应。用幽门螺杆菌刺激18小时的树突状细胞的上清液中白细胞介素-12p70的水平比白细胞介素-10高两倍，并诱导同基因脾细胞增殖和1型辅助性T细胞细胞因子释放（干扰素-γ和肿瘤坏死因子-α）。与由另一种更易被宿主防御的致胃炎病原体沃氏不动杆菌诱导的反应相比，这些反应明显更低。对整个幽门螺杆菌超声裂解物的分析揭示，幽门螺杆菌分泌一种热稳定因子，该因子特异性抑制由沃氏不动杆菌激活的树突状细胞释放白细胞介素-12，但不抑制白细胞介素-10的释放。我们的研究结果表明，树突状细胞参与宿主针对幽门螺杆菌的免疫反应，并且幽门螺杆菌对它们的抑制作用可能解释了为什么受感染宿主无法阻止细菌定植。
