Article abstract
Nature Immunology 10, 266 - 272 (2009)
Published online: 21 January 2009 | doi:10.1038/ni.1702
An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome
Tilmann Bürckstümmer1, Christoph Baumann1, Stephan Blüml1,2, Evelyn Dixit1, Gerhard Dürnberger1, Hannah Jahn1, Melanie Planyavsky1, Martin Bilban3, Jacques Colinge1, Keiryn L Bennett1 & Giulio Superti-Furga1
Abstract
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-
, 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 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 showed that AIM2 was sufficient for inflammasome activation. Our data suggest that AIM2 is a cytoplasmic DNA sensor for the inflammasome.
- Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
- Department of Rheumatology, Medical University of Vienna, Vienna A-1090, Austria.
- Department of Laboratory Medicine, Medical University of Vienna, Vienna A-1090, Austria.
Correspondence to: Giulio Superti-Furga1 e-mail: gsuperti@cemm.oeaw.ac.at
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