TOLL-LIKE RECEPTORS IN LYME NEUROBORRELIOSIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 莱姆病可能是由蜱传螺旋体伯氏疏螺旋体对神经系统的炎症作用引起的。小胶质细胞是中枢神经系统（CNS）内的常驻巨噬细胞，在启动对微生物产品的免疫应答中非常重要。此外，星形胶质细胞，主要的CNS神经胶质细胞类型，也可以有助于脑炎症。TLR（Toll样受体）被神经胶质细胞用来识别病原体相关分子模式（PAMP），介导先天性反应，并启动获得性免疫反应。在这里，我们假设，因为他们的PAMP特异性，TLR 1，2，5和9可能参与莱姆病神经疏螺旋体病的发病机制。先前的报告表明，恒河猴是唯一表现出莱姆病神经疏螺旋体病体征的动物模型。因此，我们使用恒河猴星形胶质细胞和小胶质细胞的原代培养物来确定TLR在介导对B的促炎反应中的作用。burgdorferi。通过RT-PCR定量TLR转录物和显微镜观察TLR蛋白表达的实验结果表明，小胶质细胞和星形胶质细胞对B有反应。Burgdorferi通过TLR 1/2和TLR 5。此外，我们还观察到B. Burgdorferi的小胶质细胞不仅增强TLR 1、2和5的表达，而且还增强TLR 4的表达。总之，我们的数据提供了证据的概念，星形胶质细胞和小胶质细胞TLR 1，2和5参与在体内的灵长类动物神经胶质细胞的反应B。burgdorferi。这些TLR介导的反应引起的促炎分子可能是莱姆病神经疏螺旋体病发病机制中的重要因素。基于这些结果的手稿发表在《感染与免疫》杂志上。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lyme neuroborreliosis is likely caused by inflammatory effects of the tick-borne spirochete Borrelia burgdorferi on the nervous system. Microglia, the resident macrophage cells within the central nervous system (CNS), are important in initiating an immune response to microbial products. In addition, astrocytes, the major CNS glial cell type, also can contribute to brain inflammation. TLRs (Toll-Like Receptors) are used by glial cells to recognize pathogen-associated molecular patterns (PAMPs), mediate innate responses, and initiate an acquired immune response. Here we hypothesize that because of their PAMP specificities, TLR 1, 2, 5, and 9 may be involved in the pathogenesis of Lyme neuroborreliosis. Previous reports have shown that the rhesus monkey is the only animal model to exhibit signs of Lyme neuroborreliosis. Therefore, we used primary cultures of rhesus astrocytes and microglia to determine the role of TLRs in mediating pro-inflammatory responses to B. burgdorferi. Results of experiments involving quantification of TLR transcript by RT-PCR and microscopic observation of expression of TLR protein indicate that microglia and astrocytes respond to B. burgdorferi through TLR1/2 and TLR5. In addition, we observed that phagocytosis of B. burgdorferi by microglia enhances not only the expression of TLR1, 2, and 5, but also that of TLR4. Taken together, our data provide proof of the concept that astrocyte and microglial TLR 1, 2, and 5 are involved in the in vivo response of primate glial cells to B. burgdorferi. The pro-inflammatory molecules elicited by these TLR-mediated responses could be a significant factor in the pathogenesis of Lyme neuroborreliosis. A manuscript based on these results was published in the journal Infection and Immunity.