Binding of endosomal or cytoplasmic nucleic acid ligands leads to the activation of TLR7 or TLR9 (via MyD88, IRAK and TRAF6), TLR3 (via TRIF and TRAF6) and MDA5 or RIG-I (via IPS-1 and STING). The pathways converge at the level of TBK1/IKK leading to activation of the IRF family of transcription factors, the MAPK cascade, and the NF-κB family of transcription factors, cumulatively inducing IFN-1 and inflammatory cytokine production.