Clinical manifestations of coronavirus disease 2019 (COVID-19) vary from asymptomatic virus shedding, nonspecific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The interplay between SARS-CoV-2 and these cell types remains unknown. We investigated infection and host responses of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. MoDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types and triggered significant proinflammatory cytokine/chemokine expression in MDMs but not moDCs. Investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings may explain the mild and insidious course of COVID-19 until late deterioration.

中文翻译：

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SARS-CoV-2感染的人树突状细胞中的干扰素减弱和促炎反应与STAT1磷酸化的病毒拮抗作用有关。

冠状病毒疾病2019（COVID-19）的临床表现从无症状病毒脱落，非特异性咽炎到无声缺氧和呼吸衰竭的肺炎不等。树突状细胞和巨噬细胞是前哨细胞，具有先天性和适应性免疫功能，可影响严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）的发病机理。SARS-CoV-2与这些细胞类型之间的相互作用仍然未知。我们调查了SARS-CoV-2感染的单核细胞源性树突状细胞（moDCs）和巨噬细胞（MDMs）的感染和宿主反应。MoDC和MDM允许SARS-CoV-2感染和蛋白质表达，但不支持生产性病毒复制。重要的，SARS-CoV-2在两种细胞类型中均会产生减弱的干扰素应答，并在MDM中触发了明显的促炎性细胞因子/趋化因子表达，但未在MoDC中触发。研究表明，这种在moDCs中对SARS-CoV-2减弱的免疫反应与STAT1磷酸化的病毒拮抗作用有关。这些发现可以解释COVID-19的轻度和隐匿性病程，直至晚期恶化。