Cornélie Sylvie, Hoebeke Johan, Schacht Anne-Marie, Bertin Benjamin, Vicogne Jérome, Capron Monique, Riveau Gilles
INSERM U547, Institut Pasteur de Lille, 59019 Lille Cedex, France.
J Biol Chem. 2004 Apr 9;279(15):15124-9. doi: 10.1074/jbc.M313406200. Epub 2004 Jan 20.
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.
已知细菌DNA中的胞嘧啶-磷酸-鸟嘌呤（CpG）基序可激活哺乳动物免疫系统，且这种激活被认为依赖于Toll样受体9（TLR9）信号通路。先前的研究强烈表明TLR9作为CpG基序的特异性受体发挥作用，但未提供它们相互作用的直接证据。在本研究中，我们首次证明小鼠TLR9可结合未甲基化的含CpG质粒。这种相互作用具有序列特异性，并受质粒甲基化状态的影响。此外，我们证明这种相互作用可导致表达mTLR9的细胞中NF-κB通路的激活。我们的结果为CpG-DNA与TLR9之间的相互作用提供了分子基础。
