Africa Health Research Institute, Durban, South Africa.
Department of Microbiology, Centers for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, United States.
Elife. 2018 Nov 16;7:e39169. doi: 10.7554/eLife.39169.
How () rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real time. infection induced a quiescent energy phenotype in human monocyte-derived macrophages and decelerated flux through glycolysis and the TCA cycle. In contrast, infection with the vaccine strain, BCG, or dead induced glycolytic phenotypes with greater flux. Furthermore, reduced the mitochondrial dependency on glucose and increased the mitochondrial dependency on fatty acids, shifting this dependency from endogenous fatty acids in uninfected cells to exogenous fatty acids in infected macrophages. We demonstrate how quantifiable bioenergetic parameters of the host can be used to accurately measure and track disease, which will enable rapid quantifiable assessment of drug and vaccine efficacy. Our findings uncover new paradigms for understanding the bioenergetic basis of host metabolic reprogramming by .
（）如何重塑巨噬细胞的能量代谢以促进存活的机制还知之甚少。在这里，我们使用细胞外通量分析实时地同时测量糖酵解和呼吸作用的速率。结核分枝杆菌感染诱导人单核细胞来源的巨噬细胞进入静止的能量表型，并减缓糖酵解和三羧酸（TCA）循环的通量。相比之下，感染疫苗株卡介苗（BCG）或死结核分枝杆菌诱导具有更大通量的糖酵解表型。此外，结核分枝杆菌降低了线粒体对葡萄糖的依赖性，并增加了对脂肪酸的线粒体依赖性，将这种依赖性从未感染细胞中的内源性脂肪酸转移到感染巨噬细胞中的外源性脂肪酸。我们展示了如何使用宿主可量化的生物能量学参数来准确测量和跟踪疾病，这将能够快速进行药物和疫苗疗效的可量化评估。我们的研究结果揭示了结核分枝杆菌重塑宿主代谢的新范例，理解宿主代谢重编程的能量基础。
