Borrelio burgdorferi induces TLR1 and TLR2 in human microglia and peripheral blood monocytes but differentially regulates HLA-class II expression
Borrelio burgdorferi induces TLR1 and TLR2 in human microglia and peripheral blood monocytes but differentially regulates HLA-class II expression
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DOI：
10.1097/00005072-200606000-00002
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发表时间：
2006-06-01
影响因子：
3.2
通讯作者：
Martin, Roland
中科院分区：
文献类型：
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作者：
Cassiani-Ingoni, Riccardo;Cabral, Erik S.;Martin, Roland
螺旋体伯氏疏螺旋体是莱姆病的病原体，莱姆病在多达20%的患者中引起中枢神经系统表现。我们研究了人脑小胶质细胞、胶质祖细胞、神经元、星形胶质细胞以及外周血单核细胞对B刺激的反应。burgdorferi。我们使用寡芯片来检测对形成适应性和先天性免疫应答重要的基因表达的变化。我们发现用B. Burgdorferi裂解物增加Toll样受体（TLR）1和2在除神经元外的所有细胞类型中的表达。然而，尽管单核细胞和小胶质细胞的整体基因谱相似，但只有小胶质细胞对HLA-DR，HLA-DQ的刺激做出反应，并且还共表达树突状细胞标记物CD 11-c。与此相反，大量的HLA相关分子在刺激的单核细胞的RNA和蛋白质水平上被抑制，而IL-10和TNF-α的分泌被强烈诱导。这些结果表明，通过TLR 1/2的信号传导响应于B。在血液和脑免疫细胞中，伯氏菌可引起相反的免疫调节作用，这可能在这些区室对感染的不同易感性中起作用。
The spirochete Borrelia burgdorferi is the agent of Lyme disease, which causes central nervous system manifestations in up to 20% of patients. We investigated the response of human brain microglial cells, glial progenitors, neurons, astrocytes, as well as peripheral blood monocytes to stimulation with B. burgdorferi. We used oligoarrays to detect changes in the expression of genes important for shaping adaptive and innate immune responses. We found that stimulation with B. burgdorferi lysate increased the expression of Toll-like receptors (TLRs) 1 and 2 in all cell types except neurons. However, despite similarities in global gene profiles of monocytes and microglia, only microglial cells responded to the stimulation with a robust increase in HLA-DR, HLA-DQ, and also coexpressed CD11-c, a dendritic cell marker. In contrast, a large number of HLA-related molecules were repressed at both the RNA and the protein levels in stimulated monocytes, whereas secretion of IL-10 and TNF-alpha was strongly induced. These results show that signaling through TLR1/2 in response to B. burgdorferi can elicit opposite immunoregulatory effects in blood and in brain immune cells, which could play a role in the different susceptibility of these compartments to infection.