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

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

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1113 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)501-505
Number of pages5
JournalNature
Volume448
Issue number7152
DOIs
Publication statusPublished - 2007 Jul 26

ASJC Scopus subject areas

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    Takaoka, A., Wang, Z., Choi, M. K., Yanai, H., Negishi, H., Ban, T., Lu, Y., Miyagishi, M., Kodama, T., Honda, K., Ohba, Y., & Taniguchi, T. (2007). DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature, 448(7152), 501-505. https://doi.org/10.1038/nature06013