Toll-Like Receptor 2-Independent and MyD88-Dependent the Mouse Brain
Toll-Like Receptor 2-Independent and MyD88-Dependent the Mouse Brain
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DOI：
10.1159/000225990
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发表时间：
2009-01-01
影响因子：
5.3
通讯作者：
Rivest, Serge
中科院分区：
文献类型：
--
作者：
Naert, Gaelle;Laflamme, Nathalie;Rivest, Serge
Toll样受体(Toll-like Receptor，TLRs)对病原体的快速先天免疫反应是必不可少的。虽然TLR2是革兰氏阳性细菌病原体相关分子模式的关键受体，但编码该受体的基因在暴露于TLR4配体脂多糖(LIPs)的小鼠大脑中发生了强劲的转录激活。TLR2基因的表达实际上是体内激活小胶质细胞的可靠标志，但其功能尚不清楚。本研究探讨了该受体在介导脂多糖诱导的小鼠脑内基因表达中的作用。用原位杂交和实时RT-PCR检测免疫基因。尽管小胶质细胞TLR2表达旺盛，但该受体并不通过TLR4信号调节转录活性。在注射脂多糖后6h~10d，TLR2基因缺陷小鼠和其野生型仔鼠具有相似的I kappa Bα基因表达水平和天然免疫基因的诱导。相反，在MyD88缺陷小鼠中，不再检测到核因子-kappa B活性、细胞因子、趋化因子、TLR2和CD14转录本。事实上，在这项研究中测量的大多数转录本的杂交信号在暴露于生理盐水或脂多糖的MyD88-1小鼠的大脑中是相似的。这些数据表明，虽然TLR2的转录依赖于小胶质细胞中的MyD88信号，但这种先天免疫受体并不参与对内毒素的免疫反应。另一方面，MyD88通路是内毒素诱导中枢神经系统免疫基因表达的重要途径。版权所有(C)2009 S.Karger AG，巴塞尔
Toll-like receptors (TLRs) are essential to mount a rapid innate immune reaction to pathogens. Although TLR2 is the key receptor for pathogen-associated molecular patterns from Gram-positive bacteria, a robust transcriptional activation of the gene encoding this receptor takes place in the brain of mice exposed to the TLR4 ligand lipopolysaccharide (LIPS). TLR2 gene expression is actually used as a reliable marker of activated microglia in vivo, but its functions remain unknown. The present study investigated the role of this receptor in mediating LPS-induced gene expression in the mouse brain. Immune genes were measured using both in situ hybridization and real time RT-PCR. Despite the robust microglial TLR2 expression, this receptor does not modulate transcriptional activity by TLR4 signaling. TLR2-deficient mice and their wild-type littermates had similar I kappa B alpha mRNA levels and induction of innate immune genes from 6 h to 10 days after LPS injection. In contrast, NF-kappa B activity, cytokine, chemokine, TLR2 and CD14 transcripts were no longer detected in MyD88-deficient mice. Indeed, the hybridization signal for most of the transcripts measured in this study was similar in the brain of MyD88-1-mice exposed to either saline or LPS. These data indicate that while TLR2 transcription is dependent on MyD88 signaling in microglia, this innate immune receptor is not involved in the immune response to LPS. On the other hand, MyD88 pathway is essential for the endotoxin to induce expression of immune genes in the central nervous system. Copyright (C) 2009 S. Karger AG, Basel