The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia.
The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia.
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DOI：
10.1186/1742-2094-10-88
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发表时间：
2013-07-18
影响因子：
9.3
通讯作者：
Philipp MT
中科院分区：
文献类型：
--
作者：
Ramesh G;Santana-Gould L;Inglis FM;England JD;Philipp MT
由伯氏疏螺旋体引起的莱姆性神经疏螺旋体病（LNB）会影响周围和中枢神经系统。神经根炎或神经根炎症可引起疼痛、感觉丧失和虚弱，是人类外周LNB最常见的表现。我们之前报道过感染伯氏疏螺旋体的恒河猴在背根神经节（DRG）发生根性炎和炎症，DRG中神经元和卫星胶质细胞凋亡水平升高。我们假设伯氏疏螺旋体在胶质细胞和神经元细胞中诱导炎症介质，这种炎症环境促使胶质细胞和神经元凋亡。为了模拟LNB的周围神经病变，我们用活的伯氏疏螺旋体体外培养正常恒河猴DRG组织外植体，鉴定了免疫介质和产生细胞，并通过免疫荧光染色和共聚焦显微镜验证了伯氏疏螺旋体在组织切片中的存在。我们还建立了正常成年恒河猴DRG细胞的原代培养，并与活的伯氏疏螺旋体孵育。培养上清采用多重ELISA法检测免疫介质，原位TUNEL法检测细胞凋亡。在不同浓度的抗炎药地塞米松存在和不存在的情况下，通过评估上述现象来评估炎症在介导细胞凋亡中的作用。当雪旺细胞包膜DRG背根时，我们评估了活的伯氏疏螺旋体在人雪旺细胞（HSC）培养中诱导炎症介质的潜力。体外培养的恒河猴DRG组织中，感觉神经元、卫星胶质细胞和雪旺细胞中存在CCL2和IL-6，卫星胶质细胞和雪旺细胞中存在IL-8。活体伯氏疏螺旋体诱导HSC和DRG培养物中IL-6、IL-8和CCL2水平升高，并诱导感觉神经元凋亡。地塞米松以剂量依赖性方式降低免疫介质和神经元凋亡的水平。在该模型中，伯氏疏螺旋体诱导DRG的炎症反应和神经元凋亡。这些病理生理过程可能导致LNB周围神经病变。
Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi, affects both the peripheral and the central nervous systems. Radiculitis or nerve root inflammation, which can cause pain, sensory loss, and weakness, is the most common manifestation of peripheral LNB in humans. We previously reported that rhesus monkeys infected with B. burgdorferi develop radiculitis as well as inflammation in the dorsal root ganglia (DRG), with elevated levels of neuronal and satellite glial cell apoptosis in the DRG. We hypothesized that B. burgdorferi induces inflammatory mediators in glial and neuronal cells and that this inflammatory milieu precipitates glial and neuronal apoptosis. To model peripheral neuropathy in LNB we incubated normal rhesus DRG tissue explants with live B. burgdorferi ex vivo and identified immune mediators, producer cells, and verified the presence of B. burgdorferi in tissue sections by immunofluorescence staining and confocal microscopy. We also set up primary cultures of DRG cells from normal adult rhesus macaques and incubated the cultures with live B. burgdorferi. Culture supernatants were subjected to multiplex ELISA to detect immune mediators, while the cells were evaluated for apoptosis by the in situ TUNEL assay. A role for inflammation in mediating apoptosis was assessed by evaluating the above phenomena in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone. As Schwann cells ensheath the dorsal roots of the DRG, we evaluated the potential of live B. burgdorferi to induce inflammatory mediators in human Schwann cell (HSC) cultures. Rhesus DRG tissue explants exposed to live B. burgdorferi showed localization of CCL2 and IL-6 in sensory neurons, satellite glial cells and Schwann cells while IL-8 was seen in satellite glial cells and Schwann cells. Live B. burgdorferi induced elevated levels of IL-6, IL-8 and CCL2 in HSC and DRG cultures and apoptosis of sensory neurons. Dexamethasone reduced the levels of immune mediators and neuronal apoptosis in a dose dependent manner. In this model, B. burgdorferi induced an inflammatory response and neuronal apoptosis of DRG. These pathophysiological processes could contribute to peripheral neuropathy in LNB.
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影响因子：
7.5
作者：
Bigi, S.;Aebi, C.;Steinlin, M.
通讯作者：
Steinlin, M.
影响因子：
3.7
作者：
Bremell, Daniel;Hagberg, Lars
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影响因子：
11.2
作者：
England, JD;Bohm, RP;Philipp, MT
通讯作者：
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作者：
Bernardino, Andrea L. F.;Myers, Tereance A.;Philipp, Mario T.
通讯作者：
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影响因子：
5
作者：
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通讯作者：
Boddeke, EWGM