Characterization of low-density granulocytes in COVID-19.
Characterization of low-density granulocytes in COVID-19.
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DOI：
10.1371/journal.ppat.1009721
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发表时间：
2021-07
期刊：
影响因子：
6.7
通讯作者：
Strandin T
中科院分区：
文献类型：
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作者：
Cabrera LE;Pekkarinen PT;Alander M;Nowlan KHA;Nguyen NA;Jokiranta S;Kuivanen S;Patjas A;Mero S;Pakkanen SH;Heinonen S;Kantele A;Vapalahti O;Kekäläinen E;Strandin T
严重的COVID-19的特征是广泛的肺部并发症，据信宿主免疫反应在其中发挥了作用。作为先天免疫的主要分支，嗜中性粒细胞是最早被招募到感染部位的细胞之一，在感染部位，它们的过度活化可导致肺部病理学。低密度粒细胞（LDG）是循环中性粒细胞，其数量在一些自身免疫性疾病和癌症中增加，但在急性病毒感染中特征不明显。使用流式细胞术，我们检测到与健康对照相比，急性COVID-19患者血液中LDGs显著增加。基于其表面标志物表达，COVID-19相关LDG表现出四个不同的群体，这些群体显示出粒细胞发育的不同阶段，最有可能反映紧急骨髓生成。此外，COVID-19 LDG显示与中性粒细胞的募集和激活增加有关。功能分析表明，这些细胞的免疫抑制能力，这可能有助于在急性疾病中受损的淋巴细胞反应。综上所述，我们的数据证实了COVID-19期间显著的粒细胞活化，并表明较低密度的粒细胞在疾病进展中发挥作用。SARS-COV-2和随后的COVID-19疾病的出现揭示了前所未有的需要更详细地了解急性呼吸道感染的病理机制。粒细胞是先天免疫的高度丰富的细胞，因此是急性感染的第一反应者。然而，它们的过度激活会导致人体不必要的组织损伤和有害影响。这项研究确定了COVID-19患者样本中的低密度粒细胞（LDG）群体，到目前为止，在急性感染的背景下，这一群体的描述很少。这些细胞被细分，发现主要是不成熟的表型。进一步表征显示，COVID-19 LDG是具有免疫抑制特征的表型多样性人群，这似乎与粒细胞募集和活化升高一致。总之，这些发现表明LDG可能在COVID-19疾病进展中发挥作用。
Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression. The emergence of SARS-COV-2 and the ensuing COVID-19 disease has revealed an unprecedented need to understand the pathological mechanisms of acute respiratory infections in more detail. Granulocytes are highly abundant cells of the innate immunity, and thus first responders towards acute infections. However, their excessive activation can cause unwanted tissue damage and detrimental effects in humans. This study identifies a population of low-density granulocytes (LDGs) in COVID-19 patient samples, which has been poorly described in the context of acute infections so far. These cells were subclassified and found to be mainly of immature phenotypes. Further characterization revealed COVID-19 LDGs as a phenotypically diverse population with immunosuppressive characteristics, which seemed to be in line with an elevated recruitment and activation of granulocytes. Altogether, these findings suggest LDG may play a role in COVID-19 disease progression.
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