| First Author | Kim YS | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 8 | Pages | 3283-3295 |
| PubMed ID | 28275133 | Mgi Jnum | J:247799 |
| Mgi Id | MGI:5926672 | Doi | 10.4049/jimmunol.1601920 |
| Citation | Kim YS, et al. (2017) PPAR-alpha Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism. J Immunol 198(8):3283-3295 |
| abstractText | The role of peroxisome proliferator-activated receptor alpha (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. |
