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中文摘要
翻译
这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金, 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 莱姆氏疏螺旋体病(LNB)可表现为脑膜炎、颅神经病、急性神经根神经病或罕见的脑脊髓炎。我们推测,胶质细胞在接触莱姆病病原体伯氏疏螺旋体后,会产生炎性介质,促进早期LNB的急性细胞渗透。这种炎性环境可能会增强神经胶质细胞和神经元的凋亡。将伯氏杆菌活菌接种于恒河猴枕大池,观察其对中枢神经系统(CNS)、背根神经和神经节(DRG)的炎症反应。脑脊液中IL-6、IL-8、CCL2和CXCL13最早在接种后一周升高,并伴有淋巴细胞和单核细胞增多。相反,以抗B抗体为证据的获得性免疫反应的开始。免疫后3周首次检测到伯氏杆菌C6血清抗体。脑脊液细胞球和中枢神经系统组织培养伯氏杆菌阳性。组织病理学显示急性LNB的征象:严重的多灶性软脑膜炎、神经根炎和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背根节检测到伯氏杆菌抗原。IL-6在脊髓星形胶质细胞和神经元以及感染动物的背根节神经元中均有表达。CCL2和CXCL13表达于小胶质细胞、内皮细胞、巨噬细胞和T细胞。重要的是,感染动物的背根神经节显示出明显的卫星细胞和神经元凋亡。我们的结果支持这一观点,即胶质细胞对伯氏杆菌的先天反应启动/介导了急性LNB中的炎症,并表明神经元凋亡发生在这一背景下。
英文摘要
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.
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PATHOGENESIS OF LYME NEUROBORRELIOSIS: STUDIES EX VIVO & IN VIVO
  • 批准号:
    8358068
  • 项目类别:
  • 资助金额:
    $3.72万
  • 财政年份:
    2011
  • 负责人:
    MARIO TOMAS PHILIPP
  • 依托单位:
A RHESUS MACAQUE MODEL OF STREPTOCOCCUS PNEUMONIAE CARRIAGE
  • 批准号:
    8358165
  • 项目类别:
  • 资助金额:
    $3.72万
  • 财政年份:
    2011
  • 负责人:
    MARIO TOMAS PHILIPP
  • 依托单位:
VECTOR-BORNE DISEASES CORE
  • 批准号:
    8358066
  • 项目类别:
  • 资助金额:
    $3.72万
  • 财政年份:
    2011
  • 负责人:
    MARIO TOMAS PHILIPP
  • 依托单位:
PATHOGENESIS OF LYME NEUROBORRELIOSIS IN THE RHESUS MONKEY: STUDIES IN VITRO
  • 批准号:
    8358082
  • 项目类别:
  • 资助金额:
    $3.72万
  • 财政年份:
    2011
  • 负责人:
    MARIO TOMAS PHILIPP
  • 依托单位:
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