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

Ishii, K.J, et al. Nature immunology 13: 1-9, 2005

Speaker：黃思偉                                 Time：12/14/2005 14:10~15:00

Commentator：陳舜華 老師                        Place：Room 601

Abstract：

Innate immune responses to the infection of viruses or bacteria are often triggered by specific molecular patterns such as nucleic acids of pathogens recognized by their cellular receptors like Toll-like receptors and a newly discovered helicase RIG-I. After binding specific molecules of pathogens, the receptors activate intracellular signaling pathways that induce production of proinflammatory cytokines, chemokines and type I interferons. Recently, however, more and more evidences have suggested that there is another unclear pathway different from the conventional ones able to recognize DNA including host DNA. The authors showed that transfection of double stranded B-form DNA (B-DNA) triggered the production of type I interferons and chemokines through a new pathway which is Toll-like receptor-independent. According to the experiments, they found the signaling pathway of B-DNA-induced activation of interferon regulatory factors 3 (IRF-3) and interferon-β gene promoter required the protein kinase TBK-I and IKKi (also named IKKε), but the transcription factor NF-κB was activated through the TBK-I and IKKi-independent pathway. Furthermore, another adaptor molecule termed IPS-1 linking RIG-I and TBK1 substantially joined the B-DNA-induced activation depending on both TBK-I and IKKi. In addition, B-DNA is a very common form of DNA, and macrophages without complete DNase II function may phagocytose apoptotic cells or immune complex and go through this pathway. Therefore, the TBK-I and IKKi-dependent pathway induced by B-DNA may play an important role of antiviral innate immunity and DNA-associated autoimmune diseases.

References：

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