An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome

作者：Burckstummer T; Baumann C; Bluml S; Dixit E; Durnberger G; Jahn H; Planyavsky M; Bilban M; Colinge J; Bennett K L; Superti Furga G

来源：Nature Immunology, 2009, 10(3): 266-272.

DOI：10.1038/ni.1702

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-β, 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 1β 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 1β showed that AIM2 was sufficient for inflammasome activation. Our data suggest that AIM2 is a cytoplasmic DNA sensor for the inflammasome.