PPARγ Expression and Function in Mycobacterial Infection: Roles in Lipid Metabolism, Immunity, and Bacterial Killing

Tuberculosis continues to be a global health threat, with drug resistance and HIV coinfection presenting challenges for its control. Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a highly adapted pathogen that has evolved different strategies to subvert the immune and metabolic responses of host cells. Although the significance of peroxisome proliferator-activated receptor gamma (PPAR gamma) activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPAR gamma during mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPAR gamma expression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPAR gamma expression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPAR gamma expression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPAR gamma expression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPAR gamma enhances mycobacterial killing capacity of macrophages, suggesting a role of PPAR gamma in favoring the establishment of chronic infection. Collectively, PPAR gamma is emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.