Figure 1.

Pattern recognition receptors in respiratory anti-viral immunity. (A) Toll-like receptor 3 (TLR3) signaling pathway. TLR3 mediates signaling via the adaptor protein TRIF (TIR-containing adaptor molecule-1). The TIR domain of TRIF is essential for binding to the TIR domain of TLR3. TRIF-1 is localized in the cytoplasm of resting cells, when TLR3 is activated, TRIF co-localizes with endosomal TLR3. Then TRIF dissociates from TLR3 and co-localize with downstream-signaling molecules. The serine-threonine kinases, TANK-binding kinase 1 (TBK1) and IkB kinase-related kinase-e (IKK-e) are activated once TRIF interact with them. As a result of this activation, IRF-3 is phosphorylated. TRAF3 and NF-kB-activating kinase (NAK)-associated protein 1 (NAP1) participates in the recruitment of IRF-3 kinases and in IRF-3 activation. This pathway results in the induction of type I interferons (IFNs). In addition, mitogen-activated protein kinases and (MAPK) and NF-kB pathways are activated, which results in the induction of genes involved in inflammatory responses. (B) Anti-viral immune response in airway epithelial cells mediated by pattern recognition receptors and type I interferons (IFNs). Type I IFNs produced are secreted by virus-infected cells and signal in neighboring cells through the IFN-α/β receptor complex (IFNAR). This receptor is constituted by two protein subunits called IFNAR1 and IFNAR2, which are present on the surface of cells. Interaction of type I IFNs with IFNAR in neighboring cells enhance the production of type I IFNs and other inflammatory cytokines. Activation of IFNAR by IFN-α or IFN-β leads to activation of Jak1 and Tyk2 kinases, which phosphorylate the STAT transcription factors. Then, STAT heterodimers (STAT1/STAT2) or homodimers (STAT1) are generated. IRF-9 together with phosphorylated STAT1 and STAT2 form a complex called interferon-stimulated gene factor 3 (ISGF3). This complex activates the transcription of ISGs inducing an anti-viral state in the cell.