Autophagy in Macrophages: Impacting Inflammation and Bacterial Infection

Figure 2

The downstream molecular pathways following the activation of TLR4 receptor by lipopolysaccharide (LPS) are shown. The adapter protein MyD88 is recruited by TLR4 and activates the transcription factor nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs), whose major functions include the induction of proinflammatory cytokines, chemokines, A20, and p62. TRIF is another adapter protein recruited by TLR4. It causes the activation of interferon regulatory factor-3 (IRF3) and NF-κB leading to induction of type I interferon and inflammatory cytokines. In addition, LPS-induced TLR4 activation recruits Beclin-1 through adapter proteins MyD88 and TRIF leading to formation of autophagosomes. The ubiquitination status of Beclin-1 is regulated by the TRAF6/A20 axis, which has a regulatory role in the induction of autophagosomes in response to pathogens. Pathogens can be ubiquitinated and thereby recruit autophagic adaptors like p62.