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

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Published inClinical and Diagnostic Laboratory Immunology Vol. 12; no. 5; pp. 606 - 621
Main Authors Abel, Kristina, Wang, Yichuan, Fritts, Linda, Sanchez, Eleonora, Chung, Eugene, Fitzgerald-Bocarsly, Patricia, Krieg, Arthur M., Miller, Christopher J.
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.05.2005
Subjects
Animals
Cellular Immunology
Cytokines - genetics
Dendritic Cells - drug effects
Dendritic Cells - immunology
Deoxycytosine Nucleotides
Deoxyguanosine - analogs & derivatives
DNA-Binding Proteins - analysis
DNA-Binding Proteins - genetics
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
Leukocytes, Mononuclear - immunology
Macaca mulatta
Oligodeoxyribonucleotides - administration & dosage
Oligodeoxyribonucleotides - pharmacology
Primates
Receptors, Cell Surface - analysis
Toll-Like Receptor 9
Online AccessGet full text
ISSN1556-6811
1071-412X
1556-679X
1098-6588
DOI10.1128/CDLI.12.5.606-621.2005

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Abstract Classifications Services CVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue CVI About CVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy CVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 1556-6811 Online ISSN: 1556-679X Copyright © 2014 by the American Society for Microbiology.   For an alternate route to CVI .asm.org, visit: CVI       
AbstractList 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.
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-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.
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.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.
Classifications Services CVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue CVI About CVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy CVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 1556-6811 Online ISSN: 1556-679X Copyright © 2014 by the American Society for Microbiology.   For an alternate route to CVI .asm.org, visit: CVI       
Author Linda Fritts
Patricia Fitzgerald-Bocarsly
Kristina Abel
Arthur M. Krieg
Christopher J. Miller
Eugene Chung
Eleonora Sanchez
Yichuan Wang
AuthorAffiliation Center for Comparative Medicine, 1 California National Primate Research Center, 2 Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California—Davis, Davis, California, 3 Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, New Jersey, 4 Coley Pharmaceutical Group, Inc., Wellesley, Massachusetts 5
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  surname: Wang
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  surname: Sanchez
  fullname: Sanchez, Eleonora
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  givenname: Eugene
  surname: Chung
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  surname: Fitzgerald-Bocarsly
  fullname: Fitzgerald-Bocarsly, Patricia
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– sequence: 7
  givenname: Arthur M.
  surname: Krieg
  fullname: Krieg, Arthur M.
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  givenname: Christopher J.
  surname: Miller
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/15879022$$D View this record in MEDLINE/PubMed
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Corresponding author. Mailing address: UC Davis—CCM/CNPRC, County Rd. 98/Hutchison Dr., Davis, CA 95616. Phone: (530) 754-5673. Fax: (530) 754-4411. E-mail: kabel@ucdavis.edu.
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To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as nonspecific inducers of innate immune defenses for...
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StartPage 606
SubjectTerms Animals
Cellular Immunology
Cytokines - genetics
Dendritic Cells - drug effects
Dendritic Cells - immunology
Deoxycytosine Nucleotides
Deoxyguanosine - analogs & derivatives
DNA-Binding Proteins - analysis
DNA-Binding Proteins - genetics
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
Leukocytes, Mononuclear - immunology
Macaca mulatta
Oligodeoxyribonucleotides - administration & dosage
Oligodeoxyribonucleotides - pharmacology
Primates
Receptors, Cell Surface - analysis
Toll-Like Receptor 9
Title 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
URI http://cvi.asm.org/content/12/5/606.abstract
https://www.ncbi.nlm.nih.gov/pubmed/15879022
https://www.proquest.com/docview/17494631
https://www.proquest.com/docview/67800109
https://pubmed.ncbi.nlm.nih.gov/PMC1112080
Volume 12
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