Innate immune responses are important for pathogen elimination and adaptive immune response activation. However, excess inflammation may contribute to immunopathology and disease progression, e.g. inflammation-associated hepatocellular carcinoma. Immune modulation resulting from pattern recognition receptor (PRR)-induced responses is a potential strategy for controlling immunopathology and related diseases. This study demonstrates that the mycotoxin patulin suppresses Toll-like receptor (TLR)- and RIG-I/MAVS-dependent cytokine production through GSH depletion, mitochondrial dysfunction, the activation of p62-associated mitophagy and p62-TRAF6 interaction. Blockade of autophagy restored the immunosuppressive activity of patulin and pharmmacological activation of p62-dependent mitophagy directly reduced RLR-dependent inflammatory cytokine production. These results demonstrated that p62-dependent mitophagy has an immunosuppressive role to innate immune response and might serve as a potential immunomodulatory target for inflammation-associated diseases.
Date:
2016-09
Relation:
Journal of Biological Chemistry. 2016 Sep;291(37):19299-19311.
