Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs
Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs
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DOI：
10.4049/jimmunol.173.6.3916
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发表时间：
2004-09-15
影响因子：
4.4
通讯作者：
Miller, SD
中科院分区：
文献类型：
--
作者：
Olson, JK;Miller, SD
小胶质细胞是CNS中的常驻巨噬细胞样群体。小胶质细胞保持静止，直到损伤或感染激活细胞以执行效应炎症和APC功能。我们以前的研究表明，感染Theiler鼠脑脊髓炎病毒嗜神经株的小胶质细胞分泌先天性免疫细胞因子和上调共刺激分子和MHC II类，使细胞能够将病毒和髓鞘抗原呈递给CD 4（+）T细胞。最近，TLR已被证明识别病原体相关的分子模式，并在与感染因子相互作用时启动先天免疫应答。我们研究了TLR表达脑小胶质细胞和它们的功能反应后，刺激与各种TLR激动剂。我们报告说，小鼠小胶质细胞表达mRNA的所有最近确定的TLR，TLR 1 -9，用于识别细菌和病毒的分子模式。此外，用各种TLR激动剂（包括LPS（TLR 4）、肽聚糖（TLR 2）、聚肌苷酸-聚胞苷酸（TLR 3）、CpG DNA（TLR 9））刺激静止的小胶质细胞，以及用活的Theiler鼠脑脊髓炎病毒感染，激活细胞以在mRNA和蛋白质水平上上调先天性和效应免疫细胞因子和趋化因子的独特模式。此外，TLR刺激激活了MHC II类分子和共刺激分子的上调，使小胶质细胞能够有效地将髓鞘抗原呈递给CD 4（+）T细胞。因此，小胶质细胞似乎是先天性和适应性免疫反应的独特和重要的组成部分，为CNS提供了快速有效地响应各种病原体的手段。
Microglia are the resident macrophage-like population in the CNS. Microglia remain quiescent until injury or infection activates the cells to perform effector inflammatory and APC functions. Our previous studies have shown that microglia infected with a neurotropic strain of Theiler's murine encephalomyelitis virus secreted innate immune cytokines and up-regulated costimulatory molecules and MHC class II, enabling the cells to present viral and myelin Ags to CD4(+) T cells. Recently, TLRs have been shown to recognize pathogen-associated molecular patterns and initiate innate immune responses upon interaction with infectious agents. We examined TLR expression on brain microglia and their functional responses upon stimulation with various TLR agonists. We report that mouse microglia express mRNA for all of the recently identified TLRs, TLR1-9, used for recognition of bacterial and viral molecular patterns. Furthermore, stimulation of quiescent microglia with various TLR agonists, including LPS (TLR4), peptidoglycan (TLR2), polyinosinic-polycytidylic acid (TLR3), CpG DNA (TLR9), and infection with viable Theiler's murine encephalomyelitis virus, activated the cells to up-regulate unique patterns of innate and effector immune cytokines and chemokines at the mRNA and protein levels. In addition, TLR stimulation activated up-regulation of MHC class II and costimulatory molecules, enabling the microglia to efficiently present myelin Ags to CD4(+) T cells. Thus, microglia appear to be a unique and important component of both the innate and adaptive immune response, providing the CNS with a means to rapidly and efficiently respond to a wide variety of pathogens.