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. 2019 Jul 16;10:1636. doi: 10.3389/fimmu.2019.01636

Figure 1.

Figure 1

Immune sensing pathways for RNA and DNA in the cell. The compartmentalization of nucleic acids in the cells is strictly regulated. Unrestricted RNA and DNA in the cytosol is a danger signal and can be sensed by specific receptors. The cytosolic immune receptor cyclic GMP–AMP synthetase (cGAS) detects long double-stranded DNA (dsDNA) or highly structured single-stranded DNA (ssDNA) in a special conformation. cGAS signals via STING to induce type I IFN induction. dsDNA can also be recognized by the inflammasome sensor AIM2 leading to IL-1β secretion. Cytosolic DNA is efficiently degraded by 3′ repair exonuclease 1 (TREX1) located in the outer nuclear membrane. DNAse II is restricting DNA in the endolysosome. Endosomal DNA can be detected by Toll-like receptor 9 (TLR9). TLR9 signals via interferon (IFN)-regulatory factor 7 (IRF7) and nuclear factor-κB (NF-κB) to induce type I IFN. dsRNA is detected by TLR3 and TLR7, whereas single-stranded RNA (ssRNA) is sensed by TLR7 and TLR8 in the endosome. These receptors signal via adaptor proteins to induce interferon (IFN)-regulatory factor 3 (IRF3)–IRF7 and type I IFN production and via nuclear factor-κB (NF-κB) to induce proinflammatory cytokines. The cytosolic sensors melanoma differentiation associated gene 5 (MDA5) and retinoic acid inducible gene I (RIG-I) detect dsRNA. Both signal through mitochondrial antiviral signaling protein (MAVS) to induce type I IFN production.