Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21045-900 Rio de Janeiro, RJ, Brazil.
PPAR Res. 2012;2012:383829. doi: 10.1155/2012/383829. Epub 2012 Jul 17.
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 (PPARγ) activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPARγ during mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPARγ expression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPARγ expression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPARγ expression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPARγ expression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPARγ enhances mycobacterial killing capacity of macrophages, suggesting a role of PPARγ in favoring the establishment of chronic infection. Collectively, PPARγ is emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.
结核病仍然是一个全球性的健康威胁，耐药性和 HIV 合并感染给其控制带来了挑战。结核分枝杆菌是结核病的病原体，是一种高度适应的病原体，它进化出了不同的策略来颠覆宿主细胞的免疫和代谢反应。尽管分枝杆菌激活过氧化物酶体增殖物激活受体 γ（PPARγ）的意义尚未完全理解，但最近的发现开始揭示 PPARγ 在分枝杆菌感染过程中的关键作用。在这里，我们将回顾调节分枝杆菌感染过程中 PPARγ 表达和功能的分子机制。目前的证据表明，分枝杆菌感染通过涉及模式识别受体激活的机制导致 PPARγ 表达的时间依赖性增加。分枝杆菌触发的 PPARγ 表达和激活增加导致脂滴形成增加和巨噬细胞反应下调，这表明 PPARγ 表达可能有助于分枝杆菌逃避宿主反应，作为一种逃避机制。事实上，抑制 PPARγ 增强了巨噬细胞对分枝杆菌的杀伤能力，这表明 PPARγ 在促进慢性感染的建立中发挥作用。总的来说，PPARγ 作为结核病发病机制的调节剂和辅助结核病治疗的有吸引力的靶点而出现。
