title: Mycotoxin Patulin Suppresses Innate Immune Responses by Mitochondrial Dysfunction and p62/Sequestosome-1-dependent Mitophagy.
abstract: 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-induced responses is a potential strategy for controlling immunopathology and related diseases. This study demonstrates that the mycotoxin patulin suppresses Toll-like receptor- 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 pharmacological activation of p62-dependent mitophagy directly reduced RIG-I-like receptor-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.
authors.affiliation: From the National Institute of Infectious Diseases and Vaccinology.
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Tsai
authors.affiliation: From the National Institute of Infectious Diseases and Vaccinology.
authors.forename: Yin-Chiu
authors.initials: YC
authors.lastname: Lo
authors.affiliation: From the National Institute of Infectious Diseases and Vaccinology.
authors.forename: Ming-Sian
authors.initials: MS
authors.lastname: Wu
authors.affiliation: From the National Institute of Infectious Diseases and Vaccinology, the Department of Genome Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Li
authors.affiliation: From the National Institute of Infectious Diseases and Vaccinology.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Kuo
authors.affiliation: the Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan, and.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Lai
authors.affiliation: From the National Institute of Infectious Diseases and Vaccinology.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tsai
authors.affiliation: From the National Institute of Infectious Diseases and Vaccinology.
authors.forename: Kai-Chieh
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Immunology Research Center, and.
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Chuang
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan.
authors.forename: Chun-Hsu
authors.initials: CH
authors.lastname: Yao
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan.
authors.forename: Jinq-Chyi
authors.initials: JC
authors.lastname: Lee
authors.affiliation: the Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan, and.
authors.forename: Li-Chung
authors.initials: LC
authors.lastname: Hsu
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan.
authors.forename: John T-A
authors.initials: JT
authors.lastname: Hsu
authors.affiliation: From the National Institute of Infectious Diseases and Vaccinology, the Center of Infectious Disease and Signaling Research, National Cheng-Kung University, Tainan 70101, Taiwan guannyiy@nhri.org.tw.
authors.forename: Guann-Yi
authors.initials: GY
authors.lastname: Yu
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D051379:Mice; D063306:Mitophagy / Q000187:drug effects* / Q000276:immunology; D009183:Mycotoxins / Q000494:pharmacology*; D010365:Patulin / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D000071456:Sequestosome-1 Protein / Q000276:immunology*
chemical_list: D009183:Mycotoxins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D010365:Patulin
keywords: RIG-I-like receptor (RLR); immunomodulation; mitochondria; mitophagy; mycotoxin; p62 (sequestosome 1(SQSTM1)); patulin; toll-like receptor (TLR)