PDF(Pubmed)
Abstract：
The pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern. Cell entry of SARS-CoV-2 depends on viral spike (S) proteins binding to cellular receptors (ACE2) and their subsequent priming by host cell proteases (TMPRSS2). Assessing effects of viral-induced host response factors and determining which cells are used by SARS-CoV-2 for entry might provide insights into viral transmission, add clarity to the virus\' pathogenesis, and possibly reveal therapeutic targets. Mast cells (MCs) are ubiquitously expressed tissue cells that act as immune sentinels given their ability to react specifically to pathogens at environmental interfaces, such as in the lung. Several lines of evidence suggest a critical role for MCs in SARS-CoV-2 infections based on patients\' mediator profiles, especially the \"cytokine storm\" responsible for most morbidity and mortality. In this pilot study, we demonstrated that human lung MCs (n = 3 donors) are a source of renin and that they upregulate the membrane receptor for SARS-CoV-2 (ACE2) as well as the protease required for cellular entry (TMPRSS2) under certain conditions. We hypothesized that infection of human MCs with SARS-CoV-2 may be a heretofore-unrecognized mechanism of viral pathogenesis, and further studies are required to assess this question.
摘要：
致病性严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是全球健康关注的问题。SARS-CoV-2的细胞进入取决于与细胞受体（ACE2）结合的病毒刺突（S）蛋白及其随后通过宿主细胞蛋白酶（TMPRSS2）的引发。评估病毒诱导的宿主反应因子的影响，并确定SARS-CoV-2使用哪些细胞进入可能提供对病毒传播的见解。增加病毒发病机理的清晰度，并可能揭示治疗目标。肥大细胞（MC）是广泛表达的组织细胞，由于它们能够在环境界面上对病原体做出特异性反应，因此它们充当免疫前哨。比如在肺部。几条证据表明，基于患者的介体谱，MC在SARS-CoV-2感染中的关键作用，尤其是导致大多数发病率和死亡率的“细胞因子风暴”。在这项试点研究中，我们证明了人肺MC（n=3个供体）是肾素的来源，并且它们上调SARS-CoV-2（ACE2）的膜受体以及细胞进入所需的蛋白酶（TMPRSS2）在某些条件下。我们假设SARS-CoV-2感染人类MCs可能是迄今为止尚未认识到的病毒发病机制，需要进一步的研究来评估这个问题。
