Recently, detection of bacterial DNA in cells infected with L. monocytogenes and recognition of transfected B-DNA has been shown to trigger IFN-b production. This type of response strictly requires IRF-3 [15, 34, 35, 36, 37, 38] . Such a sensing system has been suggested to represent a further mechanism of cytosolic DNA virus recognition [14, 15] and the Z-DNA binding protein 1 (Zbp1, also referred as DNA-dependent activator of IFN regulatory factors, DAI) was shown to be a candidate DNA sensor in this pathway [39] . Notably however, in a follow-up study the same group found a critical role for DAI in L-929 cells but not in mouse embryonic fibroblasts (MEFs) [40] . Furthermore, recent experiments with Zbp1/DAI knockout mice did not show the essential role of Zbp1/DAI in the induction of innate and adaptive responses to B-DNA in vivo and in macrophages, dendritic cells and MEFs in vitro [41] .