WP4655 - Cytosolic DNA-sensing pathway - Homo sapiens

As part of the innate immune system, specific cytosolic pattern recognition receptors recognize DNA from invading viruses and bacteria. These receptors have specificity for certain pathogens.
The three receptors that recognize double-stranded cytosolic DNA are CGAS (GMP-AMP Synthase), ZBP1 (DAI) and AIM. CGAS signals via STING (TREM173) and eventually results in expression of type I interferons. ZBP1 activates NFkb and IRF transcription factors which results in expression of interferons and cytokines/chemokines. Activation of AIM leads to the formation of the inflammasome complex, which activates caspase-1 and triggers a form of apoptosis known as pyroptosis.

In addition to sensors that directly detect DNA, another mechanism exists where the foreign DNA is first translated into RNA by host polymerase. The RNA is then recognized by the RNA sensor RIG-I, which leads to NFkb and IRF activation.