Department of Medical Microbiology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
J Proteome Res. 2011 Sep 2;10(9):4018-32. doi: 10.1021/pr200224x. Epub 2011 Jul 28.
Staphylococcus aureus is a dangerous opportunistic human pathogen that causes serious invasive diseases when it reaches the bloodstream. Recent studies have shown that S. aureus is highly resistant to killing by professional phagocytes and that such cells even provide a favorable environment for intracellular survival of S. aureus. Importantly, the reciprocal interactions between phagocytes and S. aureus have remained largely elusive. Here we have employed kinase profiling to define the nature and time resolution of the human THP-1 macrophage response toward S. aureus and proteomics to identify the response of S. aureus toward macrophages. The results of these studies reveal major macrophage signaling pathways triggered by S. aureus and proteomic signatures of the responses of S. aureus to macrophages. We also identify human proteins bound to S. aureus that have potential roles in bacterial killing and internalization. Most noticeably, our observations challenge the classical concept that macrophage responses are mainly mediated through Toll-like receptor 2 and NF-κB signaling and highlight the important role of the stress-activated MAP kinase signaling in orchestrating the host defense.
金黄色葡萄球菌是一种危险的机会性病原体，当它进入血液时会引起严重的侵袭性疾病。最近的研究表明，金黄色葡萄球菌对专业吞噬细胞的杀伤具有高度抗性，并且这些细胞甚至为金黄色葡萄球菌的细胞内存活提供了有利环境。重要的是，吞噬细胞与金黄色葡萄球菌之间的相互作用在很大程度上仍未被揭示。在这里，我们采用激酶谱分析来定义人类 THP-1 巨噬细胞对金黄色葡萄球菌的反应的性质和时间分辨率，并采用蛋白质组学来鉴定金黄色葡萄球菌对巨噬细胞的反应。这些研究的结果揭示了金黄色葡萄球菌触发的主要巨噬细胞信号通路以及金黄色葡萄球菌对巨噬细胞反应的蛋白质组学特征。我们还鉴定了与金黄色葡萄球菌结合的人类蛋白，这些蛋白可能在细菌杀伤和内化中发挥作用。最值得注意的是，我们的观察结果挑战了吞噬细胞反应主要通过 Toll 样受体 2 和 NF-κB 信号转导介导的经典概念，并强调了应激激活的 MAP 激酶信号转导在协调宿主防御中的重要作用。
