PPAR-alpha Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism
- 등재 SCIE, SCOPUS
- 발행기관 AMER ASSOC IMMUNOLOGISTS
- 발행년도 2017
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000144722
- 본문언어 영어
- Published As http://dx.doi.org/10.4049/jimmunol.1601920
초록/요약
The role of peroxisome proliferator-activated receptor a (PPAR-alpha) in innate host defense is largely unknown. In this study, we show that PPAR-alpha is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-alpha deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-alpha agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M. bovis bacillus Calmette-Guerin. PPAR-alpha 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-alpha activation promoted lipid catabolism and fatty acid beta-oxidation in macrophages during mycobacterial infection. Taken together, our data indicate that PPAR-alpha mediates antimicrobial responses to mycobacterial infection by inducing TFEB and lipid catabolism.
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