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

@article{citeulike:1445455, abstract = {Central to innate immunity is the sensing of pathogen-associated molecular patterns by cytosolic and membrane-associated receptors1, 2, 3, 4. In particular, DNA is a potent activator of immune responses during infection or tissue damage5, 6, 7, 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 responses8, 9, 10. Here we report on a candidate DNA sensor, previously named DLM-1 (also called Z-DNA binding protein 1 (ZBP1))11, for which biological function had remained unknown; we now propose the alternative name DAI (DNA-dependent activator of IFN-regulatory factors12). 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.}, author = {Takaoka, Akinori and Wang, Zhichao and Choi, Myoung K. and Yanai, Hideyuki and Negishi, Hideo and Ban, Tatsuma and Lu, Yan and Miyagishi, Makoto and Kodama, Tatsuhiko and Honda, Kenya and Ohba, Yusuke and Taniguchi, Tadatsugu}, citeulike-article-id = {1445455}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature06013}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature06013}, day = {08}, doi = {10.1038/nature06013}, issn = {0028-0836}, journal = {Nature}, keywords = {cytosolic\_receptor, dna, innate\_immunity}, month = {July}, number = {7152}, pages = {501--505}, posted-at = {2008-07-30 01:39:00}, priority = {0}, publisher = {Nature Publishing Group}, title = {DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response}, url = {http://dx.doi.org/10.1038/nature06013}, volume = {448}, year = {2007} }

TY - JOUR ID - citeulike:1445455 L3 - citeulike-article-id:1445455 N2 - Central to innate immunity is the sensing of pathogen-associated molecular patterns by cytosolic and membrane-associated receptors1, 2, 3, 4. In particular, DNA is a potent activator of immune responses during infection or tissue damage5, 6, 7, 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 responses8, 9, 10. Here we report on a candidate DNA sensor, previously named DLM-1 (also called Z-DNA binding protein 1 (ZBP1))11, for which biological function had remained unknown; we now propose the alternative name DAI (DNA-dependent activator of IFN-regulatory factors12). 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. IS - 7152 JF - Nature SN - 0028-0836 EP - 505 TI - DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response PB - Nature Publishing Group VL - 448 SP - 501 KW - cytosolic_receptor KW - dna KW - innate_immunity AU - Takaoka, Akinori AU - Wang, Zhichao AU - Choi, Myoung AU - Yanai, Hideyuki AU - Negishi, Hideo AU - Ban, Tatsuma AU - Lu, Yan AU - Miyagishi, Makoto AU - Kodama, Tatsuhiko AU - Honda, Kenya AU - Ohba, Yusuke AU - Taniguchi, Tadatsugu PY - 2007/07/08/ UR - http://dx.doi.org/10.1038/nature06013 ER -