DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response - PubMed (original) (raw)

. 2007 Jul 26;448(7152):501-5.

doi: 10.1038/nature06013. Epub 2007 Jul 8.

Zhichao Wang, Myoung Kwon Choi, Hideyuki Yanai, Hideo Negishi, Tatsuma Ban, Yan Lu, Makoto Miyagishi, Tatsuhiko Kodama, Kenya Honda, Yusuke Ohba, Tadatsugu Taniguchi

Affiliations

• PMID: 17618271
• DOI: 10.1038/nature06013

DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response

Akinori Takaoka et al. Nature. 2007.

Abstract

Central to innate immunity is the sensing of pathogen-associated molecular patterns by cytosolic and membrane-associated receptors. In particular, DNA is a potent activator of immune responses during infection or tissue damage, and evidence indicates that, in addition to the membrane-associated Toll-like receptor 9, an unidentified cytosolic DNA sensor(s) can activate type I interferon (IFN) and other immune responses. Here we report on a candidate DNA sensor, previously named DLM-1 (also called Z-DNA binding protein 1 (ZBP1)), for which biological function had remained unknown; we now propose the alternative name DAI (DNA-dependent activator of IFN-regulatory factors). The artificial expression of otherwise IFN-inducible DAI (DLM-1/ZBP1) in mouse fibroblasts selectively enhances the DNA-mediated induction of type I IFN and other genes involved in innate immunity. On the other hand, RNA interference of messenger RNA for DAI (DLM-1/ZBP1) in cells inhibits this gene induction programme upon stimulation by DNA from various sources. Moreover, DAI (DLM-1/ZBP1) binds to double-stranded DNA and, by doing so, enhances its association with the IRF3 transcription factor and the TBK1 serine/threonine kinase. These observations underscore an integral role of DAI (DLM-1/ZBP1) in the DNA-mediated activation of innate immune responses, and may offer new insight into the signalling mechanisms underlying DNA-associated antimicrobial immunity and autoimmune disorders.

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Comment in

• Immunology: sensing the enemy within.
  Chi H, Flavell RA. Chi H, et al. Nature. 2007 Jul 26;448(7152):423-4. doi: 10.1038/448423a. Nature. 2007. PMID: 17653183 No abstract available.

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