Université Paris Cité, Infection Antimicrobials Modelling Evolution (IAME), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
Assistance Publique - Hôpitaux de Paris (AP-HP), University Hospital Bichat-Claude Bernard, Laboratoire d'Immunologie, Paris, France.
Front Immunol. 2022 Oct 27;13:1010140. doi: 10.3389/fimmu.2022.1010140. eCollection 2022.
The emerging SARS-CoV-2 virus has affected the entire world with over 600 million confirmed cases and 6.5 million deaths as of September 2022. Since the beginning of the pandemic, several variants of SARS-CoV-2 have emerged, with different infectivity and virulence. Several studies suggest an important role of neutrophils in SARS-Cov-2 infection severity, but data about direct activation of neutrophils by the virus is scarce. Here, we studied the activation of human neutrophils by SARS-CoV-2 variants of concern (VOCs). In our work, we show that upon stimulation with SARS-Cov-2 infectious particles, human healthy resting neutrophils upregulate activation markers, degranulate IL-8, produce Reactive Oxygen Species and release Neutrophil Extracellular Traps. Neutrophil activation was dependent on TLR7/8 and IRF3/STING. We then compared the activation potential of neutrophils by SARS-CoV-2 variants and showed a significantly increased activation by the Delta variant and a decreased activation by the Omicron variant as compared to the initial strain. In this study, we demonstrate that the SARS-Cov-2 virus can directly activate neutrophils in COVID-19 and that the different VOCs had differences in neutrophil activation intensity that mirror the differences of clinical severity. These data highlight the need to address neutrophil-virus interactions as a potential target for therapeutic intervention in SARS-CoV-2 infection.
截至 2022 年 9 月，新兴的 SARS-CoV-2 病毒已影响全球超过 6 亿例确诊病例和 650 万人死亡。自疫情开始以来，已经出现了几种 SARS-CoV-2 的变体，它们具有不同的传染性和毒力。有几项研究表明，中性粒细胞在 SARS-CoV-2 感染的严重程度中起着重要作用，但关于病毒直接激活中性粒细胞的数据却很少。在这里，我们研究了 SARS-CoV-2 变体（VOCs）对人中性粒细胞的激活作用。在我们的工作中，我们表明，在受到 SARS-CoV-2 感染性颗粒的刺激后，健康的静止人中性粒细胞上调激活标志物，脱颗粒释放白细胞介素-8（IL-8），产生活性氧物质并释放中性粒细胞细胞外陷阱。中性粒细胞的激活依赖于 TLR7/8 和 IRF3/STING。然后，我们比较了 SARS-CoV-2 变体对中性粒细胞的激活潜力，结果表明与初始株相比，Delta 变体显著增加了中性粒细胞的激活，而奥密克戎变体则降低了其激活。在这项研究中，我们证明了 SARS-CoV-2 病毒可以直接激活 COVID-19 患者的中性粒细胞，并且不同的 VOCs 在中性粒细胞激活强度上存在差异，这反映了临床严重程度的差异。这些数据强调了需要解决中性粒细胞-病毒相互作用作为 SARS-CoV-2 感染治疗干预的潜在靶点。
