The Peroxisome Proliferator-Activated Receptor α- Agonist Gemfibrozil Promotes Defense Against <i>Mycobacterium abscessus</i> Infections

• Main Authors: Yi Sak Kim, Jin Kyung Kim, Bui Thi Bich Hanh, Soo Yeon Kim, Hyeon Ji Kim, Young Jae Kim, Sang Min Jeon, Cho Rong Park, Goo Taeg Oh, June-Woo Park, Jin-Man Kim, Jichan Jang, Eun-Kyeong Jo
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Cells
• Subjects: pparα; <i>mycobacterium abscessus</i>; gemfibrozil; tfeb; inflammation
• Online Access: https://www.mdpi.com/2073-4409/9/3/648

Peroxisome proliferator-activated receptor &#945; (PPAR&#945;) shows promising potential to enhance host defenses against <i>Mycobacterium tuberculosis</i> infection. Herein we evaluated the protective effect of PPAR&#945; against nontuberculous mycobacterial (NTM) infections. Using a rapidly growing NTM species, <i>Mycobacterium abscessus</i> (Mabc), we found that the intracellular bacterial load and histopathological damage were increased in PPAR&#945;-null mice in vivo. In addition, PPAR&#945; deficiency led to excessive production of proinflammatory cytokines and chemokines after infection of the lung and macrophages. Notably, administration of gemfibrozil (GEM), a PPAR&#945; activator, significantly reduced the in vivo Mabc load and inflammatory response in mice. Transcription factor EB was required for the antimicrobial response against Mabc infection. Collectively, these results suggest that manipulation of PPAR&#945; activation has promising potential as a therapeutic strategy for NTM disease.