PATHOGENESIS OF LYME NEUROBORRELIOSIS: STUDIES EX VIVO & IN VIVO
PATHOGENESIS OF LYME NEUROBORRELIOSIS: STUDIES EX VIVO & IN VIVO
批准号:
8172962
负责人:
MARIO TOMAS PHILIPP
金额:
$6.18万
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-05-01 至 2011-04-30
关键词:
AcuteAnimalsAntibodiesAntigensApoptosisAstrocytesBorrelia burgdorferiCCL2 geneCXCL13 geneCellsCellular InfiltrationCerebrospinal FluidComputer Retrieval of Information on Scientific Projects DatabaseConfocal MicroscopyCranial nerve diseasesEncephalomyelitisEndothelial CellsEnzyme-Linked Immunosorbent AssayExposure toFundingGangliaGrantHistopathologyIL8 geneImmune responseImmunofluorescence ImmunologicInflammationInflammation MediatorsInflammatoryInstitutionInterleukin-6LesionLifeLyme DiseaseLyme NeuroborreliosisLymphocyteMacaca mulattaMediatingMeningitisMicrogliaMyxoid cystNerveNeuraxisNeurogliaNeuronsPathogenesisPleocytosisRadiculitisResearchResearch PersonnelResourcesSerumSourceSpinal CordStaining methodStainsT-LymphocyteTissuesUnited States National Institutes of Healthcisterna magnain vivomacrophageneuron apoptosisresponsesatellite cellspinal nerve posterior root
中文摘要
该子项目是利用
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来源获得主要资金,
因此可以在其他CRISP条目中表示。列出的机构是
中心,不一定是研究者的机构。
莱姆病可表现为脑膜炎、颅神经病、急性神经根神经病,或罕见的脑脊髓炎。我们假设,神经胶质细胞,暴露于莱姆病病原体伯氏疏螺旋体后,产生炎症介质,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细胞和神经元的凋亡。我们接种了活的B。burgdorferi的方法注入恒河猴的小脑延髓池,并检查在中枢神经系统(CNS)和背根神经和神经节(DRG)中诱导的炎症变化。早在接种后一周,脑脊液(CSF)的ELISA显示IL-6、IL-8、CCL 2和CXCL 13升高,并伴有主要淋巴细胞和单核细胞的白细胞增多。相反,获得性免疫反应的发生,由抗B。在接种后3周后首次检测到伯氏C6血清抗体。CSF细胞团和CNS组织培养物呈B阳性。burgdorferi。组织学检查显示急性LNB体征:重度多灶性软脑膜炎、神经根炎和DRG炎性病变。免疫荧光染色和共聚焦显微镜检测B。中枢神经系统和背根神经节中的伯氏抗原。在脊髓中的星形胶质细胞和神经元中以及在感染动物的DRG中的神经元中观察到IL-6。CCL 2和CXCL 13存在于小胶质细胞以及内皮细胞、巨噬细胞和T细胞中。重要的是,感染动物的DRG显示出显著的卫星细胞和神经元凋亡。我们的研究结果支持神经胶质细胞对B. burgdorferi启动/介导急性LNB中观察到的炎症,并显示在这种情况下发生神经元凋亡。
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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:
DIAGNOSTIC PARASITOLOGY CORE
-
批准号:8358067
-
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:
TICK SALIVA INHIBITS INFLAMMATION IN MONOCYTES STIMULATED WITH B BURGDORFERI
-
批准号:8358087
-
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:
TICK SALIVA INHIBITS INFLAMMATION IN MONOCYTES STIMULATED WITH B BURGDORFERI
-
批准号:8172987
-
项目类别:
-
资助金额:$6.18万
-
财政年份:2010
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
VECTOR-BORNE DISEASES CORE
-
批准号:8172960
-
项目类别:
-
资助金额:$6.18万
-
财政年份:2010
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
PATHOGENESIS OF LYME NEUROBORRELIOSIS IN THE RHESUS MONKEY: STUDIES IN VITRO
-
批准号:8172979
-
项目类别:
-
资助金额:$6.18万
-
财政年份:2010
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
DIAGNOSTIC PARASITOLOGY CORE
-
批准号:8172961
-
项目类别:
-
资助金额:$6.18万
-
财政年份:2010
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
CHARACTERIZATION OF A MORAXELLA SPECIES THAT CAUSES EPSTAXIS IN MACAQUES
-
批准号:8173026
-
项目类别:
-
资助金额:$6.18万
-
财政年份:2010
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
PATHOGENESIS OF LYME NEUROBORRELIOSIS IN THE RHESUS MONKEY: STUDIES IN VITRO
-
批准号:7958650
-
项目类别:
-
资助金额:$5.8万
-
财政年份:2009
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
VECTOR-BORNE DISEASES CORE
-
批准号:7958625
-
项目类别:
-
资助金额:$5.8万
-
财政年份:2009
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
A RHESUS MODEL FOR COLONIZATION AND DISEASE WITH BACTERIA OF THE GENUS MORAXELLA
-
批准号:7958718
-
项目类别:
-
资助金额:$3.48万
-
财政年份:2009
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
PATHOGENESIS OF LYME NEUROBORRELIOSIS: STUDIES EX VIVO & IN VIVO
-
批准号:7958627
-
项目类别:
-
资助金额:$5.8万
-
财政年份:2009
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
DOXYCYCLINE AND MINOCYCLINE INHIBIT INFLAMMATORY RESPOSES TO B BURGDORFERI
-
批准号:7958717
-
项目类别:
-
资助金额:$5.8万
-
财政年份:2009
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
TICK SALIVA INHIBITS INFLAMMATION IN MONOCYTES STIMULATED WITH B BURGDORFERI
-
批准号:7958667
-
项目类别:
-
资助金额:$5.8万
-
财政年份:2009
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
CLOSING THE PHENOTYPIC GAP BETWEEN TRANSFORMED AND UNTRANSFORMED NEURONS
-
批准号:7958666
-
项目类别:
-
资助金额:$5.8万
-
财政年份:2009
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
TOLL-LIKE RECEPTORS IN LYME NEUROBORRELIOSIS
-
批准号:7958566
-
项目类别:
-
资助金额:$5.8万
-
财政年份:2009
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
PATHOGENESIS OF LYME NEUROBORRELIOSIS IN THE RHESUS MONKEY: STUDIES IN VITRO
-
批准号:7716290
-
项目类别:
-
资助金额:$2.41万
-
财政年份:2008
-
负责人:MARIO TOMAS PHILIPP
-
依托单位:
海外基金