CpG motifs in bacterial DNA and their immune effects.
Unmethylated CpG motifs are prevalent in bacterial but not vertebrate genomic DNAs. Oligodeoxynucleotides (ODN) containing CpG motifs activate host defense mechanisms leading to innate and acquired immune responses. The recognition of CpG motifs requires Toll-like receptor (TLR) 9, which triggers alterations in cellular redox balance and the induction of cell signaling pathways including the mitogen activated protein kinases (MAPKs) and NF kappa B. Cells that express TLR-9, which include plasmacytoid dendritic cells (PDCs) and B cells, produce Th1-like proinflammatory cytokines, interferons, and chemokines. Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators. CpG-induced activation of innate immunity protects against lethal challenge with a wide variety of pathogens, and has therapeutic activity in murine models of cancer and allergy. CpG ODN also enhance the development of acquired immune responses for prophylactic and therapeutic vaccination.
Krieg
Arthur M
AM
Department of Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA. akrieg@coleypharma.com
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001419:Bacteria / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D019175:DNA Methylation; D004269:DNA, Bacterial / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy; D009504:Neutrophils / Q000276:immunology; D020319:Oligodeoxyribonucleotides, Antisense / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
D019496:Cancer Vaccines; D004269:DNA, Bacterial; D016328:NF-kappa B; D020319:Oligodeoxyribonucleotides, Antisense; D019444:Vaccines, DNA; D020928:Mitogen-Activated Protein Kinases