title: PPAR-α Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism.
abstract: The role of peroxisome proliferator-activated receptor α (PPAR-α) in innate host defense is largely unknown. In this study, we show that PPAR-α is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-α deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-α agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense againstMycobacterium tuberculosisorM. bovisbacillus Calmette-Guérin. PPAR-α agonists regulated multiple genes involved in autophagy and lysosomal biogenesis, includingLamp2,Rab7, andTfebin bone marrow-derived macrophages. Silencing of TFEB reduced phagosomal maturation and antimicrobial responses, but increased macrophage inflammatory responses during mycobacterial infection. Moreover, PPAR-α activation promoted lipid catabolism and fatty acid β-oxidation in macrophages during mycobacterial infection. Taken together, our data indicate that PPAR-α mediates antimicrobial responses to mycobacterial infection by inducing TFEB and lipid catabolism.
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea.|Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Yi Sak
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea.|Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Molecular and Life Science, College of Science and Technology, Hanyang University, Ansan 15578, South Korea.
authors.forename: Chul-Su
authors.identifier: 0000-0003-4918-961X
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea.|Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea.|Department of Pathology, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Mingyu
authors.identifier: 0000-0003-2812-0285
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Hyo Sun
authors.initials: HS
authors.lastname: Jin
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea.|Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Sup
authors.initials: S
authors.lastname: Kim
authors.affiliation: Molecular Mechanism of Antibiotics, Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju 52828, South Korea; and.
authors.forename: Jichan
authors.initials: J
authors.lastname: Jang
authors.affiliation: Department of Life Science, Ewha Womans University, Seoul 03760, South Korea.
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.affiliation: Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea.|Department of Pathology, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea; hayoungj@cnu.ac.kr.|Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea.
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D066292:Lipid Droplets / Q000276:immunology; D050356:Lipid Metabolism / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009161:Mycobacterium; D009164:Mycobacterium Infections / Q000276:immunology*; D047493:PPAR alpha / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D047493:PPAR alpha; C484068:Tcfeb protein, mouse