TLR9 as a key receptor for the recognition of DNA.
Unmethylated DNA with CpG-motifs is recognized by Toll-like receptor 9 (TLR9) and pleiotropic immune responses are elicited. Macrophages and conventional dendritic cells (cDCs) produce proinflammatory cytokines to B/K-type CpG-DNA, whereas plasmacytoid DCs induce type I interferons to A/D-type CpG-DNA and DNA viruses. The TLR9 mediated signaling pathway is not only responsible for activation of innate immune cells, but also for mounting acquired responses. Thus, it has been attempted to exploit TLR9 ligands as a vaccine adjuvant for anti-cancer immunotherapy. Further, TLR9 mediated signaling is implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus. Nevertheless, recent studies revealed that double-stranded DNA can be recognized by intracellular receptor(s) in a TLR9-independent manner. This review will focus on the roles of TLR9 in immune responses, and its signaling pathways.
Kumagai
Yutaro
Y
Laboratory of Host Defense, WPI Immunology Frontier Research Center, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Takeuchi
Osamu
O
Akira
Shizuo
S
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D004247:DNA / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D008024:Ligands; D015398:Signal Transduction / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000502:physiology*
D007370:Interferon Type I; D008024:Ligands; D051217:Toll-Like Receptor 9; D004247:DNA