Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells.
Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells.
复制标题
DOI：
10.3389/fimmu.2021.695972
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Ochoa AC
中科院分区：
文献类型：
--
作者：
Dean MJ;Ochoa JB;Sanchez-Pino MD;Zabaleta J;Garai J;Del Valle L;Wyczechowska D;Baiamonte LB;Philbrook P;Majumder R;Vander Heide RS;Dunkenberger L;Thylur RP;Nossaman B;Roberts WM;Chapple AG;Wu J;Hicks C;Collins J;Luke B;Johnson R;Koul HK;Rees CA;Morris CR;Garcia-Diaz J;Ochoa AC
COVID-19从35%的病例无症状到20%的患者严重不等。炎症类型和程度的差异似乎决定了疾病的严重程度。最近的报告显示，在严重的COVID - 19患者中，循环单核髓源性抑制细胞（M-MDSC）增加，这种细胞会消耗精氨酸，但与呼吸系统并发症无关。我们的数据显示，粒细胞mdsc （G-MDSC）的类型、功能和转录组的差异可能部分解释了COVID-19的严重程度，特别是与肺部并发症的关联。在死于COVID-19并发症的患者肺部发现大量表达NOX-1和NOX-2（对活性氧的产生很重要）的精氨酸酶1+ G-MDSC （Arg+G-MDSC）浸润。循环中Arg+G-MDSC的增加使精氨酸减少，从而损害T细胞受体和内皮细胞功能。来自不同分期COVID-19患者的G-MDSC转录组学特征显示，无症状患者与I型干扰素（IFN）相关的途径和基因表达增加，而重症COVID-19患者与精氨酸酶产生、粒细胞脱粒和功能相关的基因表达增加。这些结果表明，无症状患者会产生保护性的I型IFN反应，而严重的COVID-19患者的炎症反应会增加，这会消耗精氨酸，损害T细胞和内皮细胞功能，并导致广泛的肺损伤。因此，抑制精氨酸酶-1和/或补充精氨酸可能对预防/治疗重症COVID-19很重要。
COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.
登录
查看更多内容
影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
28.2
作者：
Liu, Yuwei;Du, Xuebei;Zhao, Yan
通讯作者：
Zhao, Yan
影响因子：
20.3
作者：
Ramilo, Octavio;Allman, Windy;Chaussabel, Damien
通讯作者：
Chaussabel, Damien
DOI：
10.1152/ajplung.00135.2016
发表时间：
2016-11-01
影响因子：
4.9
作者：
Pouwels, Simon D.;Hesse, Laura;Heijink, Irene H.
通讯作者：
Heijink, Irene H.
影响因子：
4.2
作者：
Popovic, Petar J.;Zeh, Herbert J., III;Ochoa, Juan B.
通讯作者：
Ochoa, Juan B.