HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Deoxycytidyl-deoxyguanosine oligonucleotide classes A, B, and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear cells and distinct alpha interferon responses in TLR9-expressing rhesus monkey plasmacytoid dendritic cells.

Abstract
To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as nonspecific inducers of innate immune defenses for preventative or therapeutic interventions in infectious disease models for nonhuman primates, the present study evaluated the response of rhesus monkey peripheral blood mononuclear cells to three different synthetic CpG ODN classes by defining the cytokine gene expression patterns and by characterizing IFN-alpha/beta responses. Depending on the type and dose of CpG ODN used for stimulation, distinct gene expression patterns were induced. CpG ODN class A (CpG-A ODN) and CpG-C ODN, but not CpG-B ODN, were potent inducers of alpha interferon (IFN-alpha), and this response was due to IFN-alpha production by TLR9-positive plasmacytoid dendritic cells. Importantly, there was a dose-dependent increase in IFN-alpha responses to CpG-A ODN but a dose-dependent decrease in IFN-alpha responses by CpG-B ODN. The most sustained IFN-alpha response was induced by CpG-A ODN and was associated with a stronger induction of interferon regulatory factor 7 and the induction of several interferon-stimulated genes. In contrast, and independent of the dose, CpG-B ODN were the weakest inducers of IFN-alpha but the most potent inducers of proinflammatory cytokines. CpG-C ODN induced cytokine gene expression patterns that were intermediate between those of CpG-A and CpG-B ODN. Thus, the different types of CpG ODN induce different post-TLR9 signaling pathways that result in distinct cytokine gene expression patterns. Based on these findings, A and C class CpG ODN, but not B class CpG ODN, may be particularly suited for use as therapeutic or prophylactic antiviral interventions.
AuthorsKristina Abel, Yichuan Wang, Linda Fritts, Eleonora Sanchez, Eugene Chung, Patricia Fitzgerald-Bocarsly, Arthur M Krieg, Christopher J Miller
JournalClinical and diagnostic laboratory immunology (Clin Diagn Lab Immunol) Vol. 12 Issue 5 Pg. 606-21 (May 2005) ISSN: 1071-412X [Print] United States
PMID15879022 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cytokines
  • DNA-Binding Proteins
  • Deoxycytosine Nucleotides
  • Immunologic Factors
  • Interferon Regulatory Factor-7
  • Interferon-alpha
  • Oligodeoxyribonucleotides
  • Receptors, Cell Surface
  • Toll-Like Receptor 9
  • deoxycytidylyl-(3'-5')-deoxyguanosine
  • Deoxyguanosine
Topics
  • Animals
  • Cytokines (genetics)
  • DNA-Binding Proteins (analysis, genetics)
  • Dendritic Cells (drug effects, immunology)
  • Deoxycytosine Nucleotides
  • Deoxyguanosine (analogs & derivatives)
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation (drug effects)
  • Immunity, Innate (drug effects)
  • Immunologic Factors (pharmacology)
  • Interferon Regulatory Factor-7
  • Interferon-alpha (metabolism)
  • Leukocytes, Mononuclear (drug effects, immunology)
  • Macaca mulatta
  • Oligodeoxyribonucleotides (administration & dosage, pharmacology)
  • Receptors, Cell Surface (analysis)
  • Toll-Like Receptor 9

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: