Direct evidence that toll-like receptor 9 (TLR9) functionally binds plasmid DNA by specific cytosine-phosphate-guanine motif recognition
Direct evidence that toll-like receptor 9 (TLR9) functionally binds plasmid DNA by specific cytosine-phosphate-guanine motif recognition
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DOI：
10.1074/jbc.m313406200
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发表时间：
2004-04-09
影响因子：
4.8
通讯作者：
Riveau, G
中科院分区：
文献类型：
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作者：
Cornélie, S;Hoebeke, J;Riveau, G
细菌DNA中的胞嘧啶-磷酸-鸟氨酸(CpG)基序可以激活哺乳动物的免疫系统，这种激活被认为依赖于Toll样受体9(TLR9)信号通路。以往的研究强烈表明TLR9作为CpG基序的特异性受体参与其中，但没有提供它们相互作用的直接证据。在这项研究中，我们首次证明了小鼠TLR9结合了一个未甲基化的含CpG的质粒。这种相互作用是特定于序列的，并受质粒甲基化状态的影响。此外，我们还证明了这种相互作用导致了mTLR9表达细胞中的NF-kappaB通路的激活。我们的结果为CpG-DNA与TLR9的相互作用提供了分子基础。
Cytosine-phosphate-guanine (CpG) motifs in bacterial DNA are known to activate the mammalian immune system, and this activation is thought to depend on the Toll-like receptor 9 (TLR9) signaling pathway. Previous studies strongly suggested that TLR9 is involved as the specific receptor for CpG motifs but did not provide direct evidence of their interaction. In this study, we demonstrate for the first time that murine TLR9 binds an unmethylated CpG-containing plasmid. This interaction is sequence-specific and is influenced by the methylation status of the plasmid. Furthermore, we demonstrate that this interaction leads to the activation of the NF-kappaB pathway in mTLR9-expressing cells. Our results provide a molecular basis for the interaction between CpG-DNA and TLR9.