PPAR-α activation mediates innate host defense through induction of TFEB and lipid catabolism

Yi Sak Kim, Hye Mi Lee, Jin Kyung Kim, Chul Su Yang, Tae Sung Kim, Mingyu Jung, Hyo Sun Jin, Sup Kim, Jichan Jang, Goo Taeg Oh, Jin Man Kim, Eun Kyeong Jo

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

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 languageEnglish
Pages (from-to)3283-3295
Number of pages13
JournalJournal of Immunology
Volume198
Issue number8
DOIs
StatePublished - 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.

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