Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9.
Synthetic oligodeoxynucleotides (ODN) expressing non-methylated "CpG motifs" patterned after those present in bacterial DNA have characteristic immunomodulatory effects. CpG DNA is recognized as a pathogen-associated molecular pattern, and triggers a rapid innate immune response. CpG ODN are being harnessed for a variety of therapeutic uses, including as immune adjuvants, for cancer therapy, as anti-allergens, and as immunoprotective agents. The signal transduction pathway mediated by the engagement of CpG DNA with Toll-like receptor 9 (TLR9) is shared with other members of the TLR family. Recent studies demonstrate that formation and maturation of CpG DNA-containing endosomes are regulated by phosphatidylinositol 3 kinases and the Ras-associated GTP-binding protein, Rab5, which are essential for the initiation of TLR9-mediated signaling.
Takeshita
Fumihiko
F
Center for Biologics Evaluation and Research/Food and Drug Administration, Bldg 29A, Rm 3D10, Bethesda, MD 20892, USA.
Gursel
Ihsan
I
Ishii
Ken J
KJ
Suzuki
Koichi
K
Gursel
Mayda
M
Klinman
Dennis M
DM
D000818:Animals; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D004269:DNA, Bacterial / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011992:Endosomes / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051217:Toll-Like Receptor 9
D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9