Younes Souheil-Antoine
Department of Pathology, Pathology Advanced Translational Research (PATRU), School of Medicine, Emory University, Atlanta 30322, USA.
Immunometabolism. 2022;4(2). doi: 10.20900/immunometab20220013. Epub 2022 Apr 28.
People living with HIV (PLWH) who are immune non-responders (INR) to therapy are unable to restore their CD4 T-cell count and remain at great risk of morbidity and mortality. Here the mitochondrial defects that characterize memory CD4 T-cells in INR and causes of this mitochondrial exhaustion are reviewed. This review also describes the various reagents used to induce the expression of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), the master regulator of mitochondrial biogenesis, which can restore mitochondria fitness and CD4 T-cell proliferation in INR. Due to sustained heightened inflammation in INR, the mitochondrial network is unable to be rejuvenated and requires attenuation of mediators of inflammation to rescue mitochondria and CD4 T-cell counts in INR.
对治疗产生免疫无反应（INR）的HIV感染者（PLWH）无法恢复其CD4 T细胞计数，仍面临着很高的发病和死亡风险。本文回顾了INR中记忆CD4 T细胞所特有的线粒体缺陷以及这种线粒体耗竭的原因。本综述还描述了用于诱导过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC1α）表达的各种试剂，PGC1α是线粒体生物发生的主要调节因子，它可以恢复INR中的线粒体适应性和CD4 T细胞增殖。由于INR中炎症持续加剧，线粒体网络无法恢复活力，需要减轻炎症介质的作用，以挽救INR中的线粒体和CD4 T细胞计数。
