The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice

Figure 5

Molecular and cellular mechanisms underlying P. acnes-induced sensitization to LPS. After recognition of heat-killed P. acnes, cytoplasmic domain of TLR9 recruits MyD88 and relays a signal for nuclear translocation of NF-κB, eventually resulting in various gene expressions including IL-12 production. IL-12 is involved in the development of P. acnes-specific Th1 cells, which produce robust IFN-𝛾 in response to P. acnes. IL-12 also activates hepatic NK cells to release IFN-𝛾. IFN-𝛾 derived from Th1 cells and NK cells sensitize mice to LPS and induce their dense hepatic granuloma formation. Administration of NF-κB decoy profoundly inhibits both the LPS sensitization and the hepatic granuloma formations [16].