Recent advances in immunostimulatory CpG oligonucleotides.
The vertebrate immune system has evolved a mechanism to detect CpG motifs within microbial DNA (CpG DNA). Synthetic oligonucleotides containing CpG motifs (CpG ODNs) are potent immunomodulatory molecules and outstanding vaccine adjuvants. A number of recent findings have greatly improved our understanding of the biology of CpG DNA, and the immunological effects of CpG DNA are now recognized to be distinct in mouse and human. The plasmacytoid dendritic cell (PDC) was identified to play a pivotal role in mediating CpG-induced immune responses. So far, the B-cell is the only other immune cell subset in humans besides the PDC, equipped with the toll-like receptor-9 to detect CpG motifs. The information on these two prime CpG-sensitive cells has allowed the identification of novel CpG ODNs with distinct functional activity. Together with exciting contributions from animal studies, the way seems to be paved for the successful clinical development of this novel class of molecular therapeutics.
Rothenfusser
Simon
S
Department of Internal Medicine, Division of Clinical Pharmacology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
Tuma
Evelyn
E
Wagner
Moritz
M
Endres
Stefan
S
Hartmann
Gunther
G
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D001402:B-Lymphocytes; D018899:CpG Islands / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D009841:Oligonucleotides / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects; D051217:Toll-Like Receptor 9
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D007371:Interferon-gamma