Viral evasion of DNA-stimulated innate immune responses

Christensen, Maria H; Paludan, Søren R

ding to dimerization, nuclear translocation and activation, eventually turning on the transcription of type I IFN genes. 25, 26 Figure 1 Pattern recognition receptors sensing microbial DNA. Detection of DNA by AIM2 initiates the formation of the inflammasome complex with the adaptor protein ASC and Pro-caspase-1. Caspase-1 activation allows cleavage and maturation of the cytokines IL-1β and IL-18, which are secreted from the cell. TLR9 senses DNA in endosomes, resulting in MyD88-dependent activation of both NF-κB and IRF7 signaling pathways. cGAS binds cytosolic DNA and catalyzes the synthesis of the second messenger cGAMP, whereas IFI16 senses microbial DNA in both nuclear and cytosolic compartments. Both cGAS and IFI16 signal through the adaptor protein STING, resulting in STING dimerization and translocation from ER to ERGIC-and Golgi membrane structures. TBK1 and IRF3 recruitment to STING induces the phosphorylation and activation of IRF3. The active transcription factors NF-κB, IRF7 and IRF3 translocate to the nucleus and induce the transcription of type I IFN-and proinflammatory genes.