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RETRACTED ARTICLE

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Cell. 2000 Dec 8;103(6):909-18.

DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA.

Author information

1
The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego 9500 Gilman Drive 92093, La Jolla, CA, USA. wmchu@ucsd.edu

Abstract

Bacterial DNA and related synthetic immunostimulatory oligodeoxyribonucleotides (ISS-ODN) stimulate innate immunity. However, the molecular recognition mechanism that initiates signaling in response to bacterial DNA and ISS-ODN has not been identified. Herein, we demonstrate that administration of bacterial DNA and ISS-ODN to mice lacking the catalytic subunit of DNA-PK (DNA-PKcs) and in vitro stimulation of BMDM from these mice result in defective induction of IL-6 and IL-12. Further analysis using BMDM of IKKbeta(-/-) revealed that both DNA-PKcs and IKKbeta are essential for normal cytokine production in response to ISS-ODN or bacterial DNA. ISS-ODN and bacterial DNA activate DNA-PK, which in turn contributes to activation of IKK and NF-kappaB. These results reveal a novel role of DNA-PKcs in innate immune responses and a link between DNA repair and innate immunity.

PMID:
11136976
[Indexed for MEDLINE]
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