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. Author manuscript; available in PMC: 2024 Jun 19.
Published in final edited form as: Adv Immunol. 2024 May 3;161:53–83. doi: 10.1016/bs.ai.2024.03.001

Fig. 1. Canonical downstream signal pathways of nucleic acid sensing PRRs.

Fig. 1

PKR is activated by cytoplasmic dsRNA to phosphorylate eIF2α, leading to global translation shutdown. MDA5/RIG-I are also activated by cytoplasmic dsRNA, and through MAVS, promote the production of inflammatory cytokines via NF-kB and type I IFN via IRF-3. Cytoplasmic dsDNA activates cGAS and AIM2. Activated cGAS induces STING activation through the production of cGAMP, which in turn induces the production of inflammatory cytokines via NF-kB and type I IFN via IRF3. Activated AIM2 induces inflammasome formation and caspase 1 activation, which further cleaves and activates inflammatory cytokines (IL-Ib, IL-18) and gasdermin D, ultimately causing pyroptosis. TLR3 detects dsRNA in the endosome and induces the production of cytokines and type I IFN via TRIF. TLR 7/8 and TLR9 detect ssRNA and dsDNA in the endosome, respectively, and promote the production of inflammatory cytokines and type I IFN via MyD88.