PPARγExpression 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 γ ) activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPAR γ during mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPAR γ expression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPAR γ expression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPAR γ expression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPAR γ expression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPAR γ enhances mycobacterial killing capacity of macrophages, suggesting a role of PPAR γ in favoring the establishment of chronic infection. Collectively, PPAR γ is emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.