Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?

Figure 2 Role of innate immunity in nonalcoholic fatty liver disease progression. DAMPs and PAMPs bind to PRRs like TLRs and NLRs resulting in NAFLD progression. Binding of DAMPs and PAMPs to TLR4 and TLR9 receptors results in activation of MyD88 or TRIF signaling pathways, which activate NF-κβ and JNK signaling and induce production of cytokines like IL-1β and TNFα leading to lipid accumulation, cell injury and death in the liver. It has been demonstrated that binding of DAMPs and PAMPs to TLR2 can result in NAFLD/NASH through an undefined pathway. Binding of DAMPs and PAMPs to NLRs results in activation of NLRP3/ASC/Caspase1 through assembly of inflammasome complex, which induces production of cytokines IL-1 and IL-18 leading to hepatic inflammation and cell death.