Journal
NATURE IMMUNOLOGY
Volume 10, Issue 3, Pages 266-272Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1702
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Funding
- Austrian Academy of Sciences
- Austrian Federal Ministry of Science and Research [GZ200.145/I-VI/I/2006]
- DRAGON [GZ200.142/I-VI/ I/2006]
- European Commission [PIEF-GA-2008-220596]
- Austrian Science Fund [FWF W1205]
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Cytoplasmic DNA triggers activation of the innate immune system. Although 'downstream' signaling components have been characterized, the DNA-sensing components remain elusive. Here we present a systematic proteomics screen for proteins that associate with DNA, 'crossed' to a screen for transcripts induced by interferon-beta, which identified AIM2 as a candidate cytoplasmic DNA sensor. AIM2 showed specificity for double-stranded DNA. It also recruited the inflammasome adaptor ASC and localized to ASC 'speckles'. A decrease in AIM2 expression produced by RNA-mediated interference impaired DNA-induced maturation of interleukin 1 beta in THP-1 human monocytic cells, which indicated that endogenous AIM2 is required for DNA recognition. Reconstitution of unresponsive HEK293 cells with AIM2, ASC, caspase-1 and interleukin 1 beta showed that AIM2 was sufficient for inflammasome activation. Our data suggest that AIM2 is a cytoplasmic DNA sensor for the inflammasome.
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