Gene expression profiling of interferon-beta stimulated cells

Cytoplasmic DNA triggers the activation of the innate immune system. While downstream signaling components have been characterized, the DNA sensing components remain largely elusive. We performed a systematic proteomics screen for proteins that associate with DNA, traversed to a screen for IFN-β-induced transcripts. We identified DSIRE (DNA sensor for the IL-1β response, previously called AIM2) as a candidate cytoplasmic sensor. DSIRE showed a marked selectivity for double-stranded DNA. DSIRE can recruit the inflammasome adaptor ASC and gets redistributed to ASC speckles upon coexpression of ASC. RNAi-mediated reduction of DSIRE expression led to an impairment in IL-1β maturation. Reconstitution of unresponsive cells with DSIRE, ASC, caspase 1 and IL-1β showed that DSIRE is sufficient for inflammasome activation. Overall, our data strongly suggest that DSIRE is a cytoplasmic DNA sensor for the inflammasome. In a genomic screen, we used NIH3T3, L929 and RAW264.7 cells to identify genes that were transcriptionally regulated by IFN-β. We stimulated the cells with IFN-β for 4h, isolated the RNA and analyzed global changes in gene expression by microarray analysis. Overall, 225 genes were upregulated at least 3fold, among which numerous well-known interferon-induced genes were found