The Role of Innate Immunity in Pulmonary Infections

Figure 1

Overview of the Toll-like receptor-signaling pathway during pulmonary infections. Plasma membrane-bound TLRs (TLR1, 2, 4, 5, 6) and endosome membrane-bound TLRs (TLR9) recognize bacteria in the lungs. After bacterial recognition, TLR2 with TLR1 or TLR6 and TLR4 (in association with MD-2 and CD14) recruit TIRAP and MyD88, whereas TLR5 and TLR9 recruit MyD88. TLRs activate IRAK, followed by recruitment of TRAF6, eventually leading to activation of NF-κB and MAPKs to the nucleus and the expression of inflammatory cytokines. However, in inflammatory monocytes infected with viruses, TLR2 is activated within the endosome, followed by induction of type I IFN via unique MyD88-dependent activation of IRF3 and IRF7. In addition, TLR4 also recruits the adaptor TRIF and activates TRAF3-TBK1-IRF3 axis to produce type I IFN. TLR: Toll-like receptor; MyD88: myeloid differential protein-88; TIRAP: Toll-IL-1R domain-containing adapter protein; IRAK: IL-1 receptor-associated kinase; TRAF6: tumor necrosis factor receptor-associated factor 6; NF-κB: nuclear factor-κB; MAPKs : mitogen-activated protein kinases; TRIF: TIR domain-containing adapter inducing IFN-β; IRF: IFN regulatory factor; TRAM: TRIF-related adapter molecule; ssRNA: single-stranded RNA; dsRNA: double-stranded RNA; A. baumannii: Acinetobacter baumannii; E. coli: Escherichia coli; K. pneumoniae: Klebsiella pneumoniae; L. pneumophila: Legionella pneumophila; H. influenzae: Haemophilus influenzae; M. tuberculosis: Mycobacterium tuberculosis; P. aeruginosa: Pseudomonas aeruginosa; S. pneumoniae: Streptococcus pneumoniae; B. melitensis: Brucella melitensis; S. enterica: Salmonella enterica.