Presence of pathogen-associated DNA in cytosol induces type I IFN production. Several intracellular receptors have been implicated to some degree. These include DNA-dependent activator of interferon (IFN)-regulatory factors (DAI) (also called Z-DNA-binding protein 1, ZBP1), absent in melanoma 2 (AIM2), RNA polymerase III (Pol III), IFN-inducible protein IFI16, leucine-rich repeat flightless interacting protein-1 (LRRFIP1), DEAH-box helicases (DHX9 and DHX36), DEAD-box helicase DDX41, meiotic recombination 11 homolog A (MRE11), DNA-dependent protein kinase (DNA-PK), cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING).
Detection of cytosolic DNA requires multiple and possibly redundant sensors leading to activation of the transcription factor NF-kappaB and TBK1-mediated phosphorylation of the transcription factor IRF3. Cytosolic DNA also activates caspase-1-dependent maturation of the pro-inflammatory cytokines interleukin IL-1beta and IL-18. This pathway is mediated by AIM2.