Kranzer Katharina, Söllner Liane, Aigner Michael, Lehn Norbert, Deml Ludwig, Rehli Michael, Schneider-Brachert Wulf
Institute for Medical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
Infect Immun. 2005 Jul;73(7):4180-9. doi: 10.1128/IAI.73.7.4180-4189.2005.
Recently, we and others have shown that Helicobacter pylori induces dendritic cell (DC) activation and maturation. However, the impact of virulence factors on the interplay between DCs and H. pylori remains elusive. Therefore, we investigated the contribution of cag pathogenicity island (PAI) and VacA status on cytokine release and up-regulation of costimulatory molecules in H. pylori-treated DCs. In addition, to characterize the stimulatory capacity of H. pylori compounds in more detail, we studied the effect of formalin-inactivated and sonicated H. pylori, as well as secreted H. pylori molecules, on DCs. Incubation of DCs with viable or formalin-inactivated H. pylori induced comparable secretion of interleukin-6 (IL-6), IL-8, IL-10, IL-12, IL-1beta, and tumor necrosis factor (TNF). In contrast, IL-12 and IL-1beta release was significantly reduced in DCs treated with sonicated bacteria and secreted bacterial molecules. Treatment of sonicated H. pylori preparations with polymyxin B resulted in a significant reduction of IL-8 and IL-6 secretion, suggesting that H. pylori-derived lipopolysaccharide at least partially contributes to activation of immature DCs. In addition, the capacity of H. pylori-pulsed DCs to activate allogeneic T cells was not affected by cag PAI and VacA. Pretreatment of DC with cytochalasin D significantly inhibited secretion of IL-12, IL-1beta, and TNF, indicating that phagocytosis of H. pylori contributes to maximal activation of DCs. Taken together, our results suggest that DC activation and maturation, as well as DC-mediated T-cell activation, are independent of the cag PAI and VacA status of H. pylori.
最近,我们和其他研究人员已表明,幽门螺杆菌可诱导树突状细胞(DC)激活和成熟。然而,毒力因子对DC与幽门螺杆菌之间相互作用的影响仍不清楚。因此,我们研究了cag致病岛(PAI)和VacA状态对幽门螺杆菌处理的DC中细胞因子释放及共刺激分子上调的作用。此外,为更详细地描述幽门螺杆菌化合物的刺激能力,我们研究了经福尔马林灭活和超声处理的幽门螺杆菌以及幽门螺杆菌分泌分子对DC的影响。用活的或经福尔马林灭活的幽门螺杆菌孵育DC可诱导白细胞介素-6(IL-6)、IL-8、IL-10、IL-12、IL-1β和肿瘤坏死因子(TNF)分泌相当。相比之下,用超声处理的细菌和分泌的细菌分子处理的DC中,IL-12和IL-1β释放显著减少。用多粘菌素B处理超声处理的幽门螺杆菌制剂可导致IL-8和IL-6分泌显著减少,这表明幽门螺杆菌衍生的脂多糖至少部分有助于未成熟DC的激活。此外,幽门螺杆菌脉冲DC激活同种异体T细胞的能力不受cag PAI和VacA的影响。用细胞松弛素D预处理DC可显著抑制IL-12、IL-1β和TNF的分泌,表明幽门螺杆菌的吞噬作用有助于DC的最大激活。综上所述,我们的结果表明,DC激活和成熟以及DC介导的T细胞激活与幽门螺杆菌的cag PAI和VacA状态无关。