The Peroxisome Proliferator-Activated Receptor α- Agonist Gemfibrozil Promotes Defense Against Mycobacterium abscessus Infections

Abstract

Peroxisome proliferator-activated receptor α (PPARα) shows promising potential to enhance host defenses against <i>Mycobacterium tuberculosis</i> infection. Herein we evaluated the protective effect of PPARα 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 PPARα-null mice in vivo. In addition, PPARα deficiency led to excessive production of proinflammatory cytokines and chemokines after infection of the lung and macrophages. Notably, administration of gemfibrozil (GEM), a PPARα 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 PPARα activation has promising potential as a therapeutic strategy for NTM disease.