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A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA.
- Source :
-
Nature immunology [Nat Immunol] 2006 Jan; Vol. 7 (1), pp. 40-8. Date of Electronic Publication: 2005 Nov 13. - Publication Year :
- 2006
-
Abstract
- 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-beta through a signaling pathway that required the kinases TBK1 and IKKi, whereas there was substantial activation of transcription factor NF-kappaB 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-beta and NF-kappaB. 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.
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Animals
Chemokines metabolism
DNA, Bacterial immunology
DNA, Viral immunology
Enzyme-Linked Immunosorbent Assay
Fibroblasts immunology
Fibroblasts metabolism
Gene Expression immunology
Humans
I-kappa B Kinase
Interferon Regulatory Factor-3 metabolism
Interferon Type I metabolism
Mice
Mice, Knockout
NF-kappa B metabolism
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic immunology
Protein Serine-Threonine Kinases metabolism
RNA, Messenger analysis
Reverse Transcriptase Polymerase Chain Reaction
Transfection
DNA immunology
Signal Transduction immunology
Toll-Like Receptors immunology
Virus Diseases immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2908
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 16286919
- Full Text :
- https://doi.org/10.1038/ni1282