Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus
Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus
复制标题
DOI：
10.1046/j.1471-4159.2003.02202.x
复制
发表时间：
2004-02-01
影响因子：
4.7
通讯作者：
Kielian, T
中科院分区：
文献类型：
--
作者：
Esen, N;Tanga, FY;Kielian, T
星形胶质细胞通过释放促炎细胞因子和趋化因子，在启动和调节中枢神经系统免疫反应中发挥重要作用。在这里，我们证明了原代星形胶质细胞能够识别革兰氏阳性细菌金黄色葡萄球菌及其细胞壁产物肽聚糖(PGN)，并通过产生多种促炎介质来响应，包括白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、巨噬细胞炎症蛋白-1β(MIP-1β)、MIP-2和单核细胞趋化蛋白(MCP-1)。最近发现星形胶质细胞表达Toll样受体2(TLR2)，这是一种模式识别受体，对识别各种革兰氏阳性细菌、真菌和原生动物的结构成分非常重要。然而，TLR2在介导星形胶质细胞激活中的功能意义仍不清楚。用TLR2基因敲除小鼠的原代星形胶质细胞来评价TLR2在星形胶质细胞对金黄色葡萄球菌和PGN反应中的作用。结果表明，TLR2是金黄色葡萄球菌和PGN暴露后原代星形胶质细胞产生最大致炎细胞因子和趋化因子所必需的，但不是吞噬功能所必需的。此外，通过实时定量RT-PCR检测，这两种刺激均导致野生型星形胶质细胞TLR2 mRNA表达显著增加。这些发现表明，星形胶质细胞可能通过参与TLR2在中枢神经系统最初的抗菌免疫反应中发挥关键作用。
Astrocytes play an important role in initiating and regulating CNS immune responses through the release of proinflammatory cytokines and chemokines. Here we demonstrate that primary astrocytes are capable of recognizing the Gram-positive bacterium Staphylococcus aureus and its cell wall product peptidoglycan (PGN) and respond by producing numerous proinflammatory mediators including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1beta (MIP-1beta), MIP-2, and monocyte chemoattractant protein (MCP-1). Astrocytes have recently been shown to express Toll-like receptor 2 (TLR2), a pattern recognition receptor important for recognizing structural components of various Gram-positive bacteria, fungi, and protozoa. However, the functional significance of TLR2 in mediating astrocyte activation remains unknown. Primary astrocytes from TLR2 knockout mice were used to evaluate the role of TLR2 in astrocyte responses to S. aureus and PGN. The results demonstrate that TLR2 is essential for maximal proinflammatory cytokine and chemokine production, but not phagocytosis, in primary astrocytes following S. aureus and PGN exposure. In addition, both stimuli led to a significant increase in TLR2 mRNA expression in wild-type astrocytes as assessed by real-time quantitative RT-PCR. These findings suggest that astrocytes may play a key role in the initial antibacterial immune response in the CNS through engagement of TLR2.