PDF(Pubmed)
Abstract：
We have acquired significant knowledge regarding the pathogenesis of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). However, the underlying mechanisms responsible for disease recovery still need to be fully understood.
To gain insights into critical immune markers involved in COVID-19 etiopathogenesis, we studied the evolution of the immune profile of peripheral blood samples from patients who had recovered from COVID-19 and compared them to subjects with severe acute respiratory illness but negative for SARS-CoV-2 detection (controls). In addition, linear and clustered correlations between different parameters were determined.
The data obtained revealed a significant reduction in the frequency of inflammatory monocytes (CD14+CD16+) at hospital discharge vs. admission. Remarkably, nitric oxide (NO) production by the monocyte compartment was significantly reduced at discharge. Furthermore, interleukin (IL)-6 plasma levels were negatively correlated with the frequency of NO+CD14+CD16+ monocytes at hospital admission. However, at the time of hospital release, circulating IL-6 directly correlated with the NO production rate by monocytes. In line with these observations, we found that concomitant with NO diminution, the level of nitrotyrosine (NT) on CD8 T-cells significantly diminished at the time of hospital release. Considering that purinergic signaling constitutes another regulatory system, we analyzed the kinetics of CD39 and CD73 ectoenzyme expression in CD8 T-cells. We found that the frequency of CD39+CD8+ T-cells significantly diminished while the percentage of CD73+ cells increased at hospital discharge. In vitro, IL-6 stimulation of PBMCs from COVID-19 patients diminished the NT levels on CD8 T-cells. A clear differential expression pattern of CD39 and CD73 was observed in the NT+ vs. NT-CD8+ T-cell populations.
The results suggest that early after infection, IL-6 controls the production of NO, which regulates the levels of NT on CD8 T-cells modifying their effector functions. Intriguingly, in this cytotoxic cell population, the expression of purinergic ectoenzymes is tightly associated with the presence of nitrated surface molecules. Overall, the data obtained contribute to a better understanding of pathogenic mechanisms associated with COVID-19 outcomes.
To gain insights into critical immune markers involved in COVID-19 etiopathogenesis, we studied the evolution of the immune profile of peripheral blood samples from patients who had recovered from COVID-19 and compared them to subjects with severe acute respiratory illness but negative for SARS-CoV-2 detection (controls). In addition, linear and clustered correlations between different parameters were determined.
The data obtained revealed a significant reduction in the frequency of inflammatory monocytes (CD14+CD16+) at hospital discharge vs. admission. Remarkably, nitric oxide (NO) production by the monocyte compartment was significantly reduced at discharge. Furthermore, interleukin (IL)-6 plasma levels were negatively correlated with the frequency of NO+CD14+CD16+ monocytes at hospital admission. However, at the time of hospital release, circulating IL-6 directly correlated with the NO production rate by monocytes. In line with these observations, we found that concomitant with NO diminution, the level of nitrotyrosine (NT) on CD8 T-cells significantly diminished at the time of hospital release. Considering that purinergic signaling constitutes another regulatory system, we analyzed the kinetics of CD39 and CD73 ectoenzyme expression in CD8 T-cells. We found that the frequency of CD39+CD8+ T-cells significantly diminished while the percentage of CD73+ cells increased at hospital discharge. In vitro, IL-6 stimulation of PBMCs from COVID-19 patients diminished the NT levels on CD8 T-cells. A clear differential expression pattern of CD39 and CD73 was observed in the NT+ vs. NT-CD8+ T-cell populations.
The results suggest that early after infection, IL-6 controls the production of NO, which regulates the levels of NT on CD8 T-cells modifying their effector functions. Intriguingly, in this cytotoxic cell population, the expression of purinergic ectoenzymes is tightly associated with the presence of nitrated surface molecules. Overall, the data obtained contribute to a better understanding of pathogenic mechanisms associated with COVID-19 outcomes.
摘要：
■我们已经获得了有关冠状病毒2（SARS-CoV-2）引起的严重急性呼吸道综合症的发病机理的重要知识。然而,导致疾病康复的潜在机制仍需充分了解.
■为了深入了解与COVID-19病因相关的关键免疫标志物，我们研究了从COVID-19中康复的患者外周血样本免疫谱的演变,并将其与患有严重急性呼吸道疾病但SARS-CoV-2检测阴性的受试者(对照)进行了比较.此外,确定了不同参数之间的线性和聚类相关性。
■获得的数据显示，出院时与出院时相比，炎性单核细胞（CD14CD16）的频率显着降低admission.值得注意的是,排出时单核细胞室产生的一氧化氮（NO）显着减少。此外，入院时白细胞介素（IL）-6的血浆水平与NOCD14CD16单核细胞的频率呈负相关。然而,在医院出院的时候，循环IL-6与单核细胞的NO产生率直接相关。根据这些观察,我们发现伴随着没有减少，在医院释放时，CD8T细胞上的硝基酪氨酸（NT）水平显着降低。考虑到嘌呤能信号构成另一个调节系统，我们分析了CD8T细胞中CD39和CD73胞外酶表达的动力学。我们发现，CD39+CD8+T细胞的频率显着减少，而CD73+细胞的百分比在出院时增加。体外，IL-6刺激COVID-19患者的PBMC会降低CD8T细胞上的NT水平。在NT+与NT-CD8+T细胞群。
■结果表明，感染后早期，IL-6控制NO的产生，它调节CD8T细胞上NT的水平，从而改变其效应子功能。有趣的是，在这种细胞毒性细胞群体中，嘌呤能胞外酶的表达与硝化表面分子的存在紧密相关。总的来说,获得的数据有助于更好地了解与COVID-19结局相关的致病机制.
■为了深入了解与COVID-19病因相关的关键免疫标志物，我们研究了从COVID-19中康复的患者外周血样本免疫谱的演变,并将其与患有严重急性呼吸道疾病但SARS-CoV-2检测阴性的受试者(对照)进行了比较.此外,确定了不同参数之间的线性和聚类相关性。
■获得的数据显示，出院时与出院时相比，炎性单核细胞（CD14CD16）的频率显着降低admission.值得注意的是,排出时单核细胞室产生的一氧化氮（NO）显着减少。此外，入院时白细胞介素（IL）-6的血浆水平与NOCD14CD16单核细胞的频率呈负相关。然而,在医院出院的时候，循环IL-6与单核细胞的NO产生率直接相关。根据这些观察,我们发现伴随着没有减少，在医院释放时，CD8T细胞上的硝基酪氨酸（NT）水平显着降低。考虑到嘌呤能信号构成另一个调节系统，我们分析了CD8T细胞中CD39和CD73胞外酶表达的动力学。我们发现，CD39+CD8+T细胞的频率显着减少，而CD73+细胞的百分比在出院时增加。体外，IL-6刺激COVID-19患者的PBMC会降低CD8T细胞上的NT水平。在NT+与NT-CD8+T细胞群。
■结果表明，感染后早期，IL-6控制NO的产生，它调节CD8T细胞上NT的水平，从而改变其效应子功能。有趣的是，在这种细胞毒性细胞群体中，嘌呤能胞外酶的表达与硝化表面分子的存在紧密相关。总的来说,获得的数据有助于更好地了解与COVID-19结局相关的致病机制.
