Department of Infectious Diseases, The University of Georgia, Athens, GA, United States.
René Rachou Institute, Oswaldo Cruz Foundation, Belo Horizonte, Minas Gerais, Brazil.
Front Immunol. 2023 Oct 16;14:1255003. doi: 10.3389/fimmu.2023.1255003. eCollection 2023.
Severe forms of COVID-19, the disease caused by SARS-CoV-2, are characterized by acute respiratory distress syndrome, robust lung inflammation and death in some patients. Strong evidence has been accumulating that polymorphonuclear neutrophilic granulocytes (PMN) play an important role in the pathophysiology of severe COVID-19. SARS-CoV-2 directly induces PMN activation, mainly the release of neutrophil extracellular traps (NETs). However, the viral components inducing this PMN response remain unclear.
In this work human PMN responses were assessed in response to the spike (S) protein of two different SARS-CoV-2 variants, anti-S IgG1 antibodies or immune complexes formed by them. Production of reactive oxygen species (ROS) was measured by Diogenes-based chemiluminescence. Release of myeloperoxidase (MPO) was assessed by ELISA while secretion of a list of cytokines and growth factors was determined by high-performance multiplex cytokine assay.
We show that the SARS-CoV-2 Omicron variant S protein and anti-spike IgG1, either alone or together, stimulate ROS production in human PMNs. We also observed that the SARS-CoV-2 Wuhan S protein and anti-S IgG1 antibody together trigger MPO release from PMNs. Based on the relevance of SARS-CoV-2 and influenza co-infections, we have also investigated the impact of influenza virus infection on the previous PMN responses to S proteins or anti-S antibodies. We did not detect any significant effect of influenza co-infection on ROS generation in PMNs. Our data also show that PMN stimulation by S proteins induced the release of different chemokines, growth factors, regulatory and proinflammatory cytokines. Overall, our findings show that the SARS-CoV-2 S protein, an anti-spike IgG1 antibody or their immune complex, promote oxidative responses of PMNs in a variant-dependent manner, contributing to a better understanding of the role of PMN responses during SARS-CoV-2 infection.
由 SARS-CoV-2 引起的 COVID-19 的严重形式的特点是急性呼吸窘迫综合征、强烈的肺部炎症和一些患者死亡。越来越多的证据表明，多形核中性粒细胞（PMN）在严重 COVID-19 的病理生理学中发挥重要作用。SARS-CoV-2 直接诱导 PMN 活化，主要是中性粒细胞胞外诱捕网（NETs）的释放。然而，诱导这种 PMN 反应的病毒成分仍不清楚。
在这项工作中，我们评估了人类 PMN 对两种不同 SARS-CoV-2 变体的刺突（S）蛋白、针对它们的抗-S IgG1 抗体或免疫复合物的反应。通过基于 Diogenes 的化学发光法测量活性氧物种（ROS）的产生。通过 ELISA 评估髓过氧化物酶（MPO）的释放，同时通过高性能多重细胞因子测定法确定一系列细胞因子和生长因子的分泌。
我们表明，SARS-CoV-2 奥密克戎变体 S 蛋白和抗刺突 IgG1 无论是单独还是一起，都会刺激人 PMN 中 ROS 的产生。我们还观察到，SARS-CoV-2 武汉 S 蛋白和抗-S IgG1 抗体一起触发 PMN 中 MPO 的释放。鉴于 SARS-CoV-2 和流感的共同感染的相关性，我们还研究了流感病毒感染对之前 PMN 对 S 蛋白或抗-S 抗体反应的影响。我们没有检测到流感共同感染对 PMN 中 ROS 生成的任何显著影响。我们的数据还表明，S 蛋白刺激 PMN 诱导释放不同的趋化因子、生长因子、调节和促炎细胞因子。总的来说，我们的研究结果表明，SARS-CoV-2 S 蛋白、抗刺突 IgG1 抗体或它们的免疫复合物以变体依赖的方式促进 PMN 的氧化反应，有助于更好地理解 SARS-CoV-2 感染期间 PMN 反应的作用。
