Monocytes and Macrophages, Targets of Severe Acute Respiratory Syndrome Coronavirus 2: The Clue for Coronavirus Disease 2019 Immunoparalysis
Monocytes and Macrophages, Targets of Severe Acute Respiratory Syndrome Coronavirus 2: The Clue for Coronavirus Disease 2019 Immunoparalysis
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DOI：
10.1093/infdis/jiab044
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发表时间：
2021-06-25
影响因子：
6.4
通讯作者：
Mege, Jean-Louis
中科院分区：
文献类型：
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作者：
Boumaza, Asma;Gay, Laetitia;Mege, Jean-Louis
背景2019冠状病毒病（COVID-19）的临床表现是多形的，严重程度与年龄和合并症（如糖尿病和高血压）有关，病理生理学涉及异常免疫激活和淋巴细胞减少症。我们想知道在COVID-19期间骨髓腔室是否受到影响，以及单核细胞和巨噬细胞是否可以被严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染。来自COVID-19患者和对照的单核细胞和单核细胞衍生的巨噬细胞（MDM）感染SARS-CoV-2，并通过免疫荧光，病毒RNA提取和定量，以及总RNA提取，然后使用特异性引物，上清液细胞因子进行逆转录定量聚合酶链反应进行广泛研究。（白细胞介素6、10和1 β;干扰素β;转化生长因子β 1和肿瘤坏死因子α）和流式细胞术。评估感染前M1型与M2型或无极化的影响。SARS-CoV-2有效感染单核细胞和MDM，但它们的感染失败。感染与免疫调节性细胞因子分泌和巨噬细胞特异性转录程序的诱导相关，其特征在于M2型分子的上调。体外极化不能解释SARS-CoV-2的致病性，因为M1型和M2型MDM的感染相似。在COVID-19患者中，无论严重程度如何，单核细胞计数均降低，影响所有亚群，HLA-DR表达降低，CD 163表达增加。SARS-CoV-2驱动单核细胞和巨噬细胞诱导宿主免疫麻痹，有利于COVID-19的进展。
Background. Coronavirus disease 2019 (COVID-19) clinical expression is pleiomorphic, severity is related to age and comorbidities such as diabetes and hypertension, and pathophysiology involves aberrant immune activation and lymphopenia. We wondered if the myeloid compartment was affected during COVID-19 and if monocytes and macrophages could be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Methods. Monocytes and monocyte-derived macrophages (MDMs) from COVID-19 patients and controls were infected with SARS-CoV-2 and extensively investigated with immunofluorescence, viral RNA extraction and quantification, and total RNA extraction followed by reverse-transcription quantitative polymerase chain reaction using specific primers, supernatant cytokines (interleukins 6, 10, and 1 beta; interferon-beta; transforming growth factor-beta 1, and tumor necrosis factor-alpha), and flow cytometry. The effect of M1- vs M2-type or no polarization prior to infection was assessed.Results. SARS-CoV-2 efficiently infected monocytes and MDMs, but their infection is abortive. Infection was associated with immunoregulatory cytokines secretion and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In vitro polarization did not account for permissivity to SARS-CoV-2, since M1- and M2-type MDMs were similarly infected. In COVID-19 patients, monocytes exhibited lower counts affecting all subsets, decreased expression of HLA-DR, and increased expression of CD163, irrespective of severity.Conclusions. SARS-CoV-2 drives monocytes and macrophages to induce host immunoparalysis for the benefit of COVID-19 progression.