PATHOGENESIS OF LYME NEUROBORRELIOSIS: STUDIES EX VIVO & IN VIVO

莱姆病神经疏螺旋体病的发病机制：离体研究

基本信息

批准号：
8172962
负责人：
MARIO TOMAS PHILIPP
金额：
$ 6.18万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8172962
关键词：
Acute Animals Antibodies Antigens Apoptosis Astrocytes Borrelia burgdorferi CCL2 gene CXCL13 gene Cells Cellular Infiltration Cerebrospinal Fluid Computer Retrieval of Information on Scientific Projects Database Confocal Microscopy Cranial nerve diseases Encephalomyelitis Endothelial Cells Enzyme-Linked Immunosorbent Assay Exposure to Funding Ganglia Grant Histopathology IL8 gene Immune response Immunofluorescence Immunologic Inflammation Inflammation Mediators Inflammatory Institution Interleukin-6 Lesion Life Lyme Disease Lyme Neuroborreliosis Lymphocyte Macaca mulatta Mediating Meningitis Microglia Myxoid cyst Nerve Neuraxis Neuroglia Neurons Pathogenesis Pleocytosis Radiculitis Research Research Personnel Resources Serum Source Spinal Cord Staining method Stains T-Lymphocyte Tissues United States National Institutes of Health cisterna magna in vivo macrophage neuron apoptosis response satellite cell spinal nerve posterior root

项目摘要

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 (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG). ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. Our results support the notion that innate responses of glia to B. burgdorferi initiate/ mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。莱姆神经红细胞增多（LNB）可能表现为脑膜炎，颅神经病，急性辐射肌病变，或者很少作为脑脊髓炎。我们假设神经胶质在暴露于莱姆病剂Borrelia burgdorferi时会产生炎症介质，以促进早期LNB的急性细胞浸润。这种炎症环境可以增强神经胶质和神经元细胞凋亡。我们接种了活芽孢杆菌的活菌中的活体猕猴的水库，并检查了中枢神经系统（CNS）引起的炎症变化，背根神经和神经节（DRG）。脑脊液（CSF）的ELISA早在接种后一周就显示出IL-6，IL-8，CCL2和CCL2和CXCL13的升高，主要伴有淋巴细胞和单核细胞性细胞增多症。相比之下，抗B证明了获得的免疫反应的发作。在接种后3周后，首先可检测到汉堡C6血清抗体。 CSF细胞颗粒和中枢神经系统组织对B. burgdorferi培养阳性。组织病理学揭示了急性LNB的迹象：严重的多灶性瘦脑膜炎，辐射炎和DRG炎性病变。免疫荧光染色和共聚焦显微镜在中枢神经系统和DRG中检测到爆发芽孢杆菌抗原。在脊髓中的星形胶质细胞和神经元以及感染动物的DRG中观察到IL-6。在小胶质细胞以及内皮细胞，巨噬细胞和T细胞中发现了CCL2和CXCL13。重要的是，感染动物的DRG显示出明显的卫星细胞和神经元细胞凋亡。我们的结果支持了以下观点：神经胶质对B. burgdorferi的先天反应启动/介导急性LNB中看到的炎症，并表明在这种情况下，神经元细胞凋亡发生。