TLR2-Mediated Survival of Staphylococcus aureus in Macrophages: A Novel Bacterial Strategy against Host Innate Immunity1
TLR2-Mediated Survival of Staphylococcus aureus in Macrophages: A Novel Bacterial Strategy against Host Innate Immunity1
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DOI：
10.4049/jimmunol.178.8.4917
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发表时间：
2007-04
期刊：
影响因子：
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通讯作者：
Ikuko Watanabe;Manami Ichiki;A. Shiratsuchi;Y. Nakanishi
中科院分区：
文献类型：
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作者：
Ikuko Watanabe;Manami Ichiki;A. Shiratsuchi;Y. Nakanishi
TLR2在涉及针对微生物病原体的分泌蛋白的先天免疫应答中起模式识别受体的作用。为了研究其可能参与细胞反应，我们确定了从TLR2缺陷和野生型小鼠制备的巨噬细胞的吞噬和随后的细菌杀伤水平。TLR2缺失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，吞噬S. aureus，而E.大肠杆菌中，降低到更大程度的TLR2缺乏巨噬细胞比野生型对照。用S.金黄色葡萄球菌引起野生型巨噬细胞中JNK的激活，但在TLR2缺乏的巨噬细胞中没有，并且用JNK抑制剂预处理野生型巨噬细胞增加了吞噬的S. aureus，但同样不是E.杆菌此外，吞噬S.当用LPS预处理缺乏TLR2的巨噬细胞时，金黄色葡萄球菌以JNK依赖的方式增加。此外，JNK似乎抑制超氧化物的产生，而不是NO，在巨噬细胞。这些结果共同表明，在吞噬了S的巨噬细胞中，超氧化物水平降低。通过TLR2激活的JNK的作用，导致细菌在吞噬体中的存活延长。同样的调节对E.大肠杆菌对超氧阴离子的耐受性比S.金黄色。我们提出了一种新的细菌策略，涉及劫持先天免疫受体的巨噬细胞中的生存。
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.