Watanabe Ikuko, Ichiki Manami, Shiratsuchi Akiko, Nakanishi Yoshinobu
Graduate School of Medical Science, Kanazawa University, Japan.
J Immunol. 2007 Apr 15;178(8):4917-25. doi: 10.4049/jimmunol.178.8.4917.
TLR2 plays a role as a pattern-recognition receptor in the innate immune response involving secreted proteins against microbial pathogens. To examine its possible involvement in the cellular response, we determined the levels of the engulfment and subsequent killing of bacteria by macrophages prepared from TLR2-deficient and wild-type mice. The level of the engulfment of Staphylococcus aureus or Escherichia coli was almost the same between TLR2-lacking and wild-type macrophages. However, the colony-forming ability of engulfed S. aureus, but not of E. coli, decreased to a greater extent in TLR2-lacking macrophages than in the wild-type control. The incubation with S. aureus caused activation of JNK in wild-type macrophages but not in TLR2-lacking macrophages, and the pretreatment of wild-type macrophages with a JNK inhibitor increased the rate of killing of engulfed S. aureus, but again not of E. coli. In addition, the number of colonies formed by engulfed S. aureus increased in the JNK-dependent manner when TLR2-lacking macrophages were pretreated with LPS. Furthermore, JNK seemed to inhibit the generation of superoxide, not of NO, in macrophages. These results collectively suggested that the level of superoxide is reduced in macrophages that have engulfed S. aureus through the actions of TLR2-activated JNK, resulting in the prolonged survival of the bacterium in phagosomes. The same regulation did not influence the survival of E. coli, because this bacterium was more resistant to superoxide than S. aureus. We propose a novel bacterial strategy for survival in macrophages involving the hijacking of an innate immune receptor.
Toll样受体2（TLR2）作为一种模式识别受体，在涉及针对微生物病原体的分泌蛋白的固有免疫反应中发挥作用。为了研究其可能参与细胞反应的情况，我们测定了由TLR2缺陷型和野生型小鼠制备的巨噬细胞对细菌的吞噬水平以及随后的杀伤情况。缺乏TLR2的巨噬细胞和野生型巨噬细胞对金黄色葡萄球菌或大肠杆菌的吞噬水平几乎相同。然而，与野生型对照相比，缺乏TLR2的巨噬细胞中被吞噬的金黄色葡萄球菌的集落形成能力下降幅度更大，而被吞噬的大肠杆菌的集落形成能力则没有明显下降。与金黄色葡萄球菌共孵育可导致野生型巨噬细胞中JNK活化，但在缺乏TLR2的巨噬细胞中则不会，用JNK抑制剂预处理野生型巨噬细胞可提高被吞噬的金黄色葡萄球菌的杀伤率，但对被吞噬的大肠杆菌的杀伤率没有影响。此外，当用脂多糖（LPS）预处理缺乏TLR2的巨噬细胞时，被吞噬的金黄色葡萄球菌形成的集落数量以JNK依赖的方式增加。此外，JNK似乎抑制巨噬细胞中超氧化物的产生，而不是一氧化氮（NO）的产生。这些结果共同表明，通过TLR活化的JNK的作用，吞噬了金黄色葡萄球菌的巨噬细胞中超氧化物水平降低，导致细菌在吞噬体中存活时间延长。同样的调节对大肠杆菌的存活没有影响，因为这种细菌比金黄色葡萄球菌对超氧化物更具抗性。我们提出了一种细菌在巨噬细胞中存活的新策略，该策略涉及劫持一种固有免疫受体。
