Figures & data
Figure 1. Simplified overview of TLR4 signaling in primary lung cells. Within the alveolus LPS is recognized by the TLR4 receptor complex that is constitutively expressed by primary alveolar macrophages and epithelial cells. Upon receptor binding TLR4 sequentially activates the MyD88-dependent pathway from the plasma membrane resulting in NF-kB activation and the TRAM/TRIF-dependent pathway from the endosomal compartment leading to activation of IRF3. Cell type-specific regulation of LPS-induced TLR4 signaling in the lung is modified by microenvironmental factors, including the pulmonary surfactant lipids and proteins that partly regulate signaling through modulation of subcellular TLR4 localization. AECI, type I alveolar epithelial cells; AECII, type II alveolar epithelial cells; IFN, interferon; IL, interleukin; IRAK, interleukin-1 receptor-associated kinase; IRF, interferon regulatory factor; LPS, lipopolysaccharide; MyD88, myeloid differentiation primary response gene 88; NF-κB, nuclear factor κB; SP-A, surfactant protein A; SP-D, surfactant protein D; TIRAP, toll-interleukin 1 receptor (TIR) domain containing adaptor protein; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor-α; TRAM, TRIF-related adaptor molecule; TRIF, toll/Il-1R-domain-containing adaptor protein inducing interferon-β.
