Figure 3.

Pathogen associated molecular pattern sensing by Toll-Like Receptors. (a) In the endosomal compartment, TLRs recognize viral nucleic acid PAMPs: TLR3 recognizes dsRNAs, TLR7/8 recognizes ssRNAs, and TLR9 recognizes CpG DNA motifs. (b) On the surface of cells, TLR2 and TLR4 are known to recognize viral glycoproteins [47, 99]. TLR2/6 heterodimers help to activate the innate immune response to RSV, though the viral PAMP recognized has not been determined [100]. TLR1/2 heterodimers have been shown to recognize viral glycoproteins, though their potential role in respiratory virus infection has not been determined [99]. While there are many TLRs that recognize viral PAMPs, they signal through common adaptor molecules, including MyD88, MAL, TRAM, and TRIF. The TLR adaptor molecules signal through the IKKɛ/TBK1 complex and the IKKα/IKKβ/IKKγ complex similarly to RLRs, but can also recruit an IRAK-1/IRAK4/TRAF6 complex capable of activating the transcription factors IRF3, IRF7, and NF-κB. Activation of these transcription factors leads to the transcription of Type I IFNs and proinflammatory cytokines. Due to the considerable crosstalk between TLR and RLR signaling, it is difficult to discriminate between transcriptional products generated by the two sensor families, but it is likely that both play an important role in the innate immune response to SARS-CoV infection.