Figure 2.

TLR response and Atgs. (A) Atgs control endotoxin-induced IL-1β production. TLR4 triggers both MyD88- and TRIF-dependent signaling pathways after sensing LPS. The IKK-α–IKK-β–NEMO complex mediates the activation of the transcription factor NF-κB, which in turn induces the transcription of proinflammatory cytokines and pro–IL-1β. The TBK1–IKK-i complex mediates the activation of the transcription factor IRF3, which then induces the transcription of type I IFNs and IFN-inducible genes. In autophagy-deficient cells, high levels of ROS are generated, which mediate TRIF-dependent caspase-1 activation, resulting in the processing of IL-1β. However, in wild-type macrophages, limited amounts of IL-1β are induced by LPS as the result of a lack of ROS generation. (B) Atgs contribute to TLR-dependent elimination of pathogens. After detection of the fungal cell wall component zymosan, TLR2 induces the maturation of phagosomes, leading to the elimination of the fungus. Atgs such as Atg5, Atg7, and PI3K are involved in the fusion of phagosomes with lysosomes. (C) Ligands for TLR7 such as ssRNA and imiquimod induce the formation of autophagosomes via MyD88, an essential adaptor molecule, and promote the elimination of Bacillus Calmette-Guerin. LPS, a ligand for TLR4, induces the formation of autophagosomes via the TRIF-p38 signaling axis, leading to the elimination of Mycobacterial bacilli. Atgs such as Atg5, beclin, and PI3K are required for the formation of autophagosomes by TLR stimulation.