Metabolic programs define dysfunctional immune responses in severe COVID-19 patients
Metabolic programs define dysfunctional immune responses in severe COVID-19 patients
复制标题
代谢程序定义了重症 COVID-19 患者免疫反应功能失调
DOI：
10.1101/2020.09.10.20186064
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
J. Powell
中科院分区：
文献类型：
--
作者：
E. Thompson;K. Cascino;A. Ordonez;Weiqiang Zhou;A. Vaghasia;A. Hamacher;N. Brady;Im;Rulin Wang;A. Rosenberg;Michael Delannoy;R. Rothman;K. Fenstermacher;L. Sauer;K. Shaw;E. Bloch;A. Redd;A. Tobian;M. Horton;Kellie N. Smith;A. Pekosz;F. D’Alessio;S. Yegnasubramanian;Hongkai Ji;A. Cox;J. Powell
通过询问急性感染的COVID-19患者的外周血单核细胞（PBMC）中的代谢程序，我们鉴定了新的和不同的免疫细胞亚群。我们的研究鉴定了表达高H3 K27 me 3和电压依赖性阴离子通道（VDAC）的T细胞的非克隆群体，其具有线粒体功能障碍和对细胞死亡的易感性增加。这些细胞的特征是畸形的线粒体和增加的细胞质细胞色素c，通过阻止VDAC聚集或阻断半胱天冬酶激活来抑制细胞凋亡。此外，我们观察到己糖激酶II+多形核髓源性抑制细胞（PMN-MDSC）的显着增加。虽然在其他病毒感染患者的PBMC中也发现了PMN-MDSC，但己糖激酶II+ PMN-MDSC仅在中度或重度疾病的急性COVID-19患者中发现。最后，我们鉴定了一群表达高肉毒碱棕榈酰转移酶I（CPT 1a）和VDAC的单核细胞MDSC（M-MDSC），它们存在于急性COVID-19患者的PBMC中，但不存在于恢复的COVID-19患者中，并且它们的存在与疾病的严重程度相关。总的来说，这些独特的免疫细胞群提供了对SARS-CoV-2感染发病机制的深入了解，并提供了预测和跟踪疾病严重程度的方法，以及设计和评估新治疗方案的机会。
By interrogating metabolic programs in the peripheral blood mononuclear cells (PBMC) of acutely infected COVID-19 patients, we identified novel and distinct immune cell subsets Our studies identified a non-clonal population of T cells expressing high H3K27me3 and voltage-dependent anion channel (VDAC) with mitochondrial dysfunction and increased susceptibility to cell death. Characterized by dysmorphic mitochondria and increased cytoplasmic cytochrome c, apoptosis of these cells was inhibited by preventing VDAC aggregation or blocking caspase activation. Further, we observed a marked increase in Hexokinase II+ polymorphonuclear-myeloid derived suppressor cells (PMN-MDSC). While PMN-MDSC were also found in the PBMC of patients with other viral infections, the Hexokinase II+ PMN-MDSC were found exclusively in the acute COVID-19 patients with moderate or severe disease. Finally, we identified a population of monocytic MDSC (M-MDSC) expressing high carnitine palmitoyltransferase I (CPT1a) and VDAC, which were present in the PBMC of the acute COVID-19 patients, but not recovered COVID-19 patients and whose presence correlated with severity of disease. Overall, these unique populations of immune cells provide insight into the pathogenesis of SARS-CoV-2 infection and provide a means to predict and track disease severity as well as an opportunity to design and evaluate novel therapeutic regimens.
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影响因子：
11.8
作者：
Cox, AL;Netski, DM;Thomas, DL
通讯作者：
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