Metabolic programs define dysfunctional immune responses in severe COVID-19 patients.
Metabolic programs define dysfunctional immune responses in severe COVID-19 patients.
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DOI：
10.1016/j.celrep.2021.108863
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发表时间：
2021-03-16
期刊：
影响因子：
8.8
通讯作者：
Powell JD
中科院分区：
文献类型：
--
作者：
Thompson EA;Cascino K;Ordonez AA;Zhou W;Vaghasia A;Hamacher-Brady A;Brady NR;Sun IH;Wang R;Rosenberg AZ;Delannoy M;Rothman R;Fenstermacher K;Sauer L;Shaw-Saliba K;Bloch EM;Redd AD;Tobian AAR;Horton M;Smith K;Pekosz A;D'Alessio FR;Yegnasubramanian S;Ji H;Cox AL;Powell JD
目前尚不清楚为什么一些SARS-CoV-2患者容易治愈感染，而另一些患者则会患上严重疾病。通过与其他病毒感染相比，对2019冠状病毒病（COVID-19）重症和康复患者免疫细胞的代谢程序进行询问，我们确定了一种独特的T细胞群。这些T细胞表达增加的电压依赖性阴离子通道1 (VDAC1)，并伴有与线粒体功能障碍和凋亡相关的基因程序和功能特征。这些细胞的百分比在老年患者中增加，并与淋巴细胞减少有关。重要的是，通过靶向VDAC1的寡聚化或阻断caspase活性，可以在体外抑制T细胞凋亡。我们还观察到具有COVID-19特异性独特代谢表型的髓源性抑制细胞的扩增，它们的存在区分了严重和轻度疾病。总的来说，这些代谢表型的识别提供了对急性COVID-19患者功能失调免疫反应的深入了解，并提供了预测和跟踪疾病严重程度和/或设计代谢治疗方案的手段。具有独特代谢谱的T细胞在急性COVID-19中扩增，这些T细胞容易发生线粒体凋亡，与淋巴细胞减少有关，代谢不同的髓源性抑制细胞在急性COVID-19中增加，这些M-MDSCs的存在与疾病严重程度相关，与COVID-19疾病严重程度相关的确切免疫缺陷尚未确定。基于免疫代谢谱，Thompson等人确定了与疾病严重程度相关的独特的T细胞和骨髓细胞群。这些发现强调了代谢途径可能是COVID-19的治疗靶点。
It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T cells. These T cells express increased Voltage-Dependent Anion Channel 1 (VDAC1), accompanied by gene programs and functional characteristics linked to mitochondrial dysfunction and apoptosis. The percentage of these cells increases in elderly patients and correlates with lymphopenia. Importantly, T cell apoptosis is inhibited in vitro by targeting the oligomerization of VDAC1 or blocking caspase activity. We also observe an expansion of myeloid-derived suppressor cells with unique metabolic phenotypes specific to COVID-19, and their presence distinguishes severe from mild disease. Overall, the identification of these metabolic phenotypes provides insight into the dysfunctional immune response in acutely ill COVID-19 patients and provides a means to predict and track disease severity and/or design metabolic therapeutic regimens. T cells with a unique metabolic profile are expanded in acute COVID-19 These T cells are prone to mitochondrial apoptosis, correlating with lymphopenia Metabolically distinct myeloid-derived suppressor cells increase in acute COVID-19 The presence of these M-MDSCs in acute COVID-19 correlates with disease severity The precise immunological defects that correlate with disease severity in COVID-19 have yet to be determined. Based on immune-metabolic profiling, Thompson et al. identify unique populations of T cells and myeloid cells that correlate with disease severity. These findings highlight metabolic pathways as possible therapeutic targets for COVID-19.
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影响因子：
4
作者：
Camara AKS;Zhou Y;Wen PC;Tajkhorshid E;Kwok WM
通讯作者：
Kwok WM
影响因子：
24.8
作者：
Kuri-Cervantes, Leticia;Pampena, Maria Betina;Betts, Michael R.
通讯作者：
Betts, Michael R.
影响因子：
4.8
作者：
Ben-Hail, Danya;Begas-Shvartz, Racheli;Shoshan-Barmatz, Varda
通讯作者：
Shoshan-Barmatz, Varda
DOI：
10.1126/science.abc6261
发表时间：
2020-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arunachalam PS;Wimmers F;Mok CKP;Perera RAPM;Scott M;Hagan T;Sigal N;Feng Y;Bristow L;Tak-Yin Tsang O;Wagh D;Coller J;Pellegrini KL;Kazmin D;Alaaeddine G;Leung WS;Chan JMC;Chik TSH;Choi CYC;Huerta C;Paine McCullough M;Lv H;Anderson E;Edupuganti S;Upadhyay AA;Bosinger SE;Maecker HT;Khatri P;Rouphael N;Peiris M;Pulendran B
通讯作者：
Pulendran B
影响因子：
64.5
作者：
Buck MD;Sowell RT;Kaech SM;Pearce EL
通讯作者：
Pearce EL