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

Kristina Abel, Yichuan Wang, Linda Fritts, Eleonora Sanchez, Eugene Chung, Patricia Fitzgerald-Bocarsly, Arthur M. Krieg, Chris J Miller

Research output: Contribution to journalArticle

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Abstract

To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as non-specific 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-α/β 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-α), and this response was due to IFN-α production by TLR9-positive plasmacytoid dendritic cells. Importantly, there was a dose-dependent increase in IFN-α responses to CpG-A ODN but a dose-dependent decrease in IFN-α responses by CpG-B ODN. The most sustained IFN-α 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-α 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.

Original languageEnglish (US)
Pages (from-to)606-621
Number of pages16
JournalClinical and Diagnostic Laboratory Immunology
Volume12
Issue number5
DOIs
StatePublished - May 2005

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Deoxyguanosine
Macaca mulatta
Interferon-alpha
Gene expression
Oligonucleotides
Dendritic Cells
Interferons
Blood Cells
Blood
Cytokines
Gene Expression
Interferon Regulatory Factor-7
Interferon Inducers
Therapeutic Uses
Primates
Antiviral Agents
Communicable Diseases
Genes

ASJC Scopus subject areas

  • Microbiology (medical)
  • Immunology and Allergy
  • Clinical Biochemistry
  • Immunology

Cite this

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. / Abel, Kristina; Wang, Yichuan; Fritts, Linda; Sanchez, Eleonora; Chung, Eugene; Fitzgerald-Bocarsly, Patricia; Krieg, Arthur M.; Miller, Chris J.

In: Clinical and Diagnostic Laboratory Immunology, Vol. 12, No. 5, 05.2005, p. 606-621.

Research output: Contribution to journalArticle

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abstract = "To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as non-specific 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-α/β 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-α), and this response was due to IFN-α production by TLR9-positive plasmacytoid dendritic cells. Importantly, there was a dose-dependent increase in IFN-α responses to CpG-A ODN but a dose-dependent decrease in IFN-α responses by CpG-B ODN. The most sustained IFN-α 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-α 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.",
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AU - Wang, Yichuan

AU - Fritts, Linda

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AU - Fitzgerald-Bocarsly, Patricia

AU - Krieg, Arthur M.

AU - Miller, Chris J

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