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 against Mycobacterium tuberculosis or M. bovis bacillus Calmette-Gue'rin. PPAR-α agonists regulated multiple genes involved in autophagy and lysosomal biogenesis, including Lamp2, Rab7, and Tfeb in 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 b-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.
Original language | English |
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Pages (from-to) | 3283-3295 |
Number of pages | 13 |
Journal | Journal of Immunology |
Volume | 198 |
Issue number | 8 |
DOIs | |
State | Published - 15 Apr 2017 |
Bibliographical note
Funding Information:This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, Ministry of Health and Welfare, Republic of Korea (HI15C0395), by the National Research Foundation grant funded by the Korean government (MSIP) (NRF-2015M3C9A2054326) at Chungnam National University
Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved.