Direct evidence that toll-like receptor 9 (TLR9) functionally binds plasmid DNA by specific cytosine-phosphate-guanine motif recognition.
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.
Cornélie
Sylvie
S
INSERM U547, Institut Pasteur de Lille, 59019 Lille Cedex, France.
Hoebeke
Johan
J
Schacht
Anne-Marie
AM
Bertin
Benjamin
B
Vicogne
Jérome
J
Capron
Monique
M
Riveau
Gilles
G
D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D018899:CpG Islands; D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D007313:Insecta; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D020349:Surface Plasmon Resonance; D013997:Time Factors; D051217:Toll-Like Receptor 9; D014162:Transfection
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D004247:DNA