Figure 4.

Cytosolic DNA sensors and their signaling pathways. DNA present in the cytoplasm derived from either hosts or microbes are recognized by various kinds of DNA sensors. DDX41, DAI, DNA-PK, IFI16, MRE11, and cGAS recognize dsDNA and induce type I IFN production through STING via TBK1- and IRF3-dependent pathways. AT-rich dsDNA recognized by RNA polymerase III is transcribed to 5′-triphosphate RNA to be further sensed by RIG-I to induce IPS-1-dependent type I production; similarly, H2B also recognizes dsDNA and signals through IPS1. LRRFIP1 binds both dsDNA and dsRNA and activates β-catenin, which enhances a TBK1-independent and IRF3-dependent IFN-β transcription. DHX9 and DHX36 are MyD88-dependent DNA sensors. AIM2 and nuclear IFI16 can form inflammasomes together with ASC and caspase-1 on recognition of dsDNA to mediate a caspase-1-dependent cleavage of IL-1β and IL-18 from pro-IL-1β and pro-1L-18. Finally, Ku-70 recognizes dsDNA to induce IRF1/IRF7-dependent type III IFN.