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 language | English |
|---|---|
| Pages (from-to) | 501-505 |
| Number of pages | 5 |
| Journal | Nature |
| Volume | 448 |
| Issue number | 7152 |
| DOIs | |
| Publication status | Published - 2007 Jul 26 |
| Externally published | Yes |
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Cite this
DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. / Takaoka, Akinori; Wang, Zhichao; Choi, Myoung Kwon; Yanai, Hideyuki; Negishi, Hideo; Ban, Tatsuma; Lu, Yan; Miyagishi, Makoto; Kodama, Tatsuhiko; Honda, Kenya; Ohba, Yusuke; Taniguchi, Tadatsugu.
In: Nature, Vol. 448, No. 7152, 26.07.2007, p. 501-505.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response
AU - Takaoka, Akinori
AU - Wang, Zhichao
AU - Choi, Myoung Kwon
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 - 2007/7/26
Y1 - 2007/7/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34547143110&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547143110&partnerID=8YFLogxK
U2 - 10.1038/nature06013
DO - 10.1038/nature06013
M3 - Article
C2 - 17618271
AN - SCOPUS:34547143110
VL - 448
SP - 501
EP - 505
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 7152
ER -