FIG. 4.

Cytosolic DNA sensors. A large panel of sensors is dedicated to the detection of DNA in the cytosol. Among them, Ku70 induces IFN-λ, DHX9 induces proinflammatory cytokines, and DHX36, DAI, RNA polymerase III, and IFI16 induce production of type I IFNs and proinflammatory cytokines. RNA polymerase III acts by transcribing DNA into RNA molecules bearing uncapped 5′-triphosphates, which bind RIG-I and engage the IPS-1/STING pathway (see Fig. 3). Another sensor, LRRFIP1, binds DNA (or dsRNA) and activates β-catenin, which migrates to the nucleus and potentiates IFNB gene transcription by promoting recruitment of the acetyltransferase p300 to the IFN enhanceosome. In addition, IFI16 and AIM2 induce the assembly of an inflammasome by recruiting pro-caspases via the adaptor ASC, thus leading to caspase-mediated activation and secretion of IL-1β and IL-18. IFI16 (and perhaps other sensors) may recognize DNA in the nucleus and then migrate to the cytoplasm to initiate signal activation.