Toll-like receptor 9 (TLR9) recognizes unmethylated cytosine-guanine dinucleotide (CpG) sequences in DNA and activates immunity by inducing proinflammatory cytokines and interferons. The finding that TLR9 recognizes CpG-DNA is deduced primarily from the results of experiments using DNA with phosphorothioate backbone. Unmethlated CpG sites frequently appear in the DNA of pathogens; they are almost never found in mammalian DNA. Therefore, TLR9 recognition of unmethlated CpG is believed to be related to host defense mechanism. However, proinflammatory cytokines and interferons are also induced by the interaction between TLR9 and DNA consisting entirely of phosphodiester backbone, which multimerize by self-assembly and do not contain CpG. Furthermore, proinflammatory cytokines and interferons are also induced by the formation of complexes of cationic nanoparticles and DNA having only phosphodiester backbone. Therefore, it has now clear that TLR9 recognition of naturally-occurring DNA consisting entirely of phosphodiester backbone does not depend on base sequence. It is possible that TLR9fs base sequence-independent recognition of DNA is involved in the activation of not only host defense systems, but also autoimmunity. For activation of autoimmunity by TLR9, it is believed that the formation of biomolecule complexes rather than nanoparticle complexes is involved.
Key words: CpG DNA, Toll-like receptor 9, immunostimulation, cationic nanoparticles