Three classes of PRRs for RNA virus recognition.
ssRNA from viruses is recognized by TLR7 in pDCs, whereas dsRNA is detected by TLR3 in cDCs. TLR7 and TLR3 trigger signaling cascades via the adaptors MyD88 and TRIF, respectively. RIG-I and MDA5 recruit another adaptor protein, IPS-1. TRIF and IPS-1 share signaling molecules for phosphorylation of IRF-3 and IRF-7 by TBK1/IKK/i. MyD88-dependent signaling directly activates IRF-7 in pDCs. Phosphorylated IRF-3 and IRF-7 activate the expression of type I IFN genes. Simultaneously, TLRs and RLRs induce the translocation of NF-κB to induce the expression of cytokine genes via distinct adaptor proteins. On the other hand, one of the NLR proteins, NALP3, detects the presence of dsRNA and induces the catalytic activity of caspase-1 via an adaptor, ASC. Caspase-1 is essential for cleavage of pro-IL-1β to the mature form.