Regulation of CpG-induced immune activation by suppressive oligodeoxynucleotides.
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated "CpG motifs" stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing "suppressive" motifs. This work explores the rules governing cellular recognition of stimulatory and suppressive motifs, and the resultant modulation of the immune system. Results suggest that both CpG and suppressive ODN may find use as therapeutic agents.
Klinman
Dennis M
DM
Section of Retroviral Research, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. Klinman@cber.fda.gov
Zeuner
Rainald
R
Yamada
Hiroshi
H
Gursel
Mayda
M
Currie
Debbie
D
Gursel
Ihsan
I
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D001168:Arthritis / Q000517:prevention & control; D018899:CpG Islands / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005260:Female; D007107:Immune System / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D051217:Toll-Like Receptor 9
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9