Oligodeoxyribonucleotides with 5′-ACGT-3′ or 5′-TCGA-3′ Sequence Induce Production of Interferons

Yamamoto, Saburo; Yamamoto, Toshiko; Tokunaga, Tohru

doi:10.1007/978-3-642-59672-8_2

Cited by 12 publications

(9 citation statements)

References 64 publications

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“…One of the main effects of CpG DNA (12) and poly(I:C) (13, 14) is the induction of type I IFNs. In addition to the essential role of type I IFNs in antiviral innate immunity (15), they appear to be key cytokines to induce effective adaptive immunity due to their pleiotropic effects on various types of immune cells (15)(16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Distinct CpG DNA and Polyinosinic-Polycytidylic Acid Double-Stranded RNA, Respectively, Stimulate CD11c− Type 2 Dendritic Cell Precursors and CD11c+ Dendritic Cells to Produce Type I IFN

Kadowaki

Антоненко

Liu

2001

The Journal of Immunology

244

185

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Two classes of nucleic acids, bacterial DNA containing unmethylated CpG motifs and dsRNA in viruses, induce the production of type I IFN that contributes to the immunostimulatory effects of these microbial molecules. Thus, it is important to determine which cells produce type I IFN in response to CpG DNA and dsRNA. CD4+CD11c− type 2 dendritic cell precursors (pre-DC2) were identified as the main producers of type I IFN in human blood in response to viruses. Here we asked whether pre-DC2 also produce type I IFN in response to CpG DNA and dsRNA. Oligodeoxynucleotides containing particular palindromic CpG motifs induced pre-DC2, but not CD11c+ blood DC or monocytes, to produce IFN-α. In contrast, a synthetic dsRNA, polyinosinic polycytidylic-acid, induced CD11c+ DC, but not pre-DC2 or monocytes, to produce IFN-αβ. These data indicate that CpG DNA and polyinosinic-polycytidylic acid stimulate different types of cells to produce type I IFN and that it is important to select oligodeoxynucleotides containing particular CpG motifs to induce pre-DC2 to produce type I IFN, which may play a key role in the strong adjuvant effects of CpG DNA.

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Section: Discussionmentioning

confidence: 99%

Distinct CpG DNA and Polyinosinic-Polycytidylic Acid Double-Stranded RNA, Respectively, Stimulate CD11c− Type 2 Dendritic Cell Precursors and CD11c+ Dendritic Cells to Produce Type I IFN

Kadowaki

Антоненко

Liu

2001

The Journal of Immunology

244

185

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“…Yamamoto et al reported that ODNs failed to improve survival in mice challenged with influenza [53]. In addition, the authors were unable to protect against high-dose challenge with Yersinia enterolitica and could not induce sterilising immunity against respiratory syncytial virus.…”

Section: As Seen Inmentioning

confidence: 99%

Use of CpG oligodeoxynucleotides as immunoprotective agents

Klinman

2004

Expert Opinion on Biological Therapy

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Single-stranded oligodeoxynucleotides (ODNs) synthesised to express unmethylated 'CpG motifs' mimic the ability of bacterial DNA to trigger the innate immune system. CpG ODNs stimulate cells that express Toll-like receptor 9, initiating an immunomodulatory cascade resulting in the activation of B and T lymphocytes, natural killer cells, monocytes, macrophages and dendritic cells. CpG ODNs improve the host's ability to resist infection by accelerating and improving the induction of an innate and then adaptive immune response, characterised by the production of Th1 and pro-inflammatory cytokines, chemokines and polyreactive antibodies. Studies in rodents and non-human primates demonstrate that CpG ODNs can protect the host against bacterial, viral, fungal and parasitic infections. CpG-induced protection develops rapidly but persists for only a few weeks. Preclinical and clinical trials suggest that CpG ODNs can be used safely to activate the human immune system.

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“…Immunostimulatory DNA sequence oligodeoxynucleotides (ISS ODNs), generally containing 15-25 bases, are capable of inducing innate immune responses. The basis for host recognition of microbial, but not mammalian, DNA is the high frequency of non-methylated CpG dinucleotides present in the DNA of most microorganisms [9]. Stimulation with ISS initiates a cascade of cytokine induction and cellular changes that are responsible for the potent and varied activities of ISS, including promotion of increased resistance to a variety of infectious microorganisms, the development of greatly enhanced T cell and antibody responses, and preferential induction of T cells of the Th1 type [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Intranasal administration of peptide antigens of HIV with mucosal adjuvant CpG ODN coentrapped in microparticles enhances the mucosal and systemic immune responses

Pun¹,

Bhat²,

Mohan³

et al. 2009

International Immunopharmacology

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Oligodeoxyribonucleotides with 5′-ACGT-3′ or 5′-TCGA-3′ Sequence Induce Production of Interferons

Cited by 12 publications

References 64 publications

Distinct CpG DNA and Polyinosinic-Polycytidylic Acid Double-Stranded RNA, Respectively, Stimulate CD11c− Type 2 Dendritic Cell Precursors and CD11c+ Dendritic Cells to Produce Type I IFN

Distinct CpG DNA and Polyinosinic-Polycytidylic Acid Double-Stranded RNA, Respectively, Stimulate CD11c− Type 2 Dendritic Cell Precursors and CD11c+ Dendritic Cells to Produce Type I IFN

Use of CpG oligodeoxynucleotides as immunoprotective agents

Intranasal administration of peptide antigens of HIV with mucosal adjuvant CpG ODN coentrapped in microparticles enhances the mucosal and systemic immune responses

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