2. Academic Validation
  3. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome

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

  • Nat Immunol. 2009 Mar;10(3):266-72. doi: 10.1038/ni.1702.
Tilmann Bürckstümmer 1,  Christoph Baumann,  Stephan Blüml,  Evelyn Dixit,  Gerhard Dürnberger,  Hannah Jahn,  Melanie Planyavsky,  Martin Bilban,  Jacques Colinge,  Keiryn L Bennett,  Giulio Superti-Furga
Affiliations

Affiliation

  • 1 Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
PMID: 19158679 DOI: 10.1038/ni.1702
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-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 1beta 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 1beta 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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