A Toll-like receptor–independent antiviral response induced by double-stranded B-form DNA

An Erratum to this article was published on 01 April 2006

This article has been updated


The innate immune system recognizes nucleic acids during infection or tissue damage; however, the mechanisms of intracellular recognition of DNA have not been fully elucidated. Here we show that intracellular administration of double-stranded B-form DNA (B-DNA) triggered antiviral responses including production of type I interferons and chemokines independently of Toll-like receptors or the helicase RIG-I. B-DNA activated transcription factor IRF3 and the promoter of the gene encoding interferon-β through a signaling pathway that required the kinases TBK1 and IKKi, whereas there was substantial activation of transcription factor NF-κB independent of both TBK and IKKi. IPS-1, an adaptor molecule linking RIG-I and TBK1, was involved in B-DNA-induced activation of interferon-β and NF-κB. B-DNA signaling by this pathway conferred resistance to viral infection in a way dependent on both TBK1 and IKKi. These results suggest that both TBK1 and IKKi are required for innate immune activation by B-DNA, which might be important in antiviral innate immunity and other DNA-associated immune disorders.

*Note: In the version of this article initially published, the GEO database accession number is missing. This should be the final subsection of Methods, as follows: code. GEO: microarray data, GSE4171. The error has been corrected in the PDF version of the article.

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Figure 1: Activation of MEFs by dsDNA to produce type I interferons and chemokines.
Figure 2: B-DNA activation requires TBK1 and, in part, IKKi, but not TLRs or RIG-I.
Figure 3: B-DNA-induced IFN-β and NF-κB requires IPS-1.
Figure 4: Effects of B-DNA-induced EF activation on viral infection.
Figure 5: B-DNA stimulates DCs via TBK1.

Change history

  • 10 March 2006

    In the version of this article initially published, the GEO database accession number is missing. This should be the final subsection of Methods, as follows: Accession code. GEO: microarray data, GSE4171. The error has been corrected in the PDF version of the article.


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We thank Y. Fujita for technical support; K. Matsui, T. Hirotani and H. Kumar for support; K. Sakurai and N. Shimada for circular dichroism measurement of the DNA-lipid complex; T. Abe and Y. Matsuura for providing VSV; H. Shirota for discussions; T. Majima and K. Kawai for providing Z-DNA and for discussions; and other members of Exploratory Research for Advanced Technology, Japan Science and Technology Agency and the Department of Host Defense, Osaka University, for support.

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Correspondence to Shizuo Akira.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Mda-5 is not involved in B-DNA-induced type-I IFN and chemokine inductions. (PDF 122 kb)

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Ishii, K., Coban, C., Kato, H. et al. A Toll-like receptor–independent antiviral response induced by double-stranded B-form DNA. Nat Immunol 7, 40–48 (2006). https://doi.org/10.1038/ni1282

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