Mayer IgA Nephropathy Laboratory, University of Leicester, Leicester, United Kingdom
mSphere. 2020 Jun 24;5(3):e00367-20. doi: 10.1128/mSphere.00367-20.
COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.
COVID-19 常与导致肺部或多器官损伤的过度炎症有关。导致过度炎症的免疫病理机制正在研究中,并不断更新。在这里,我们使用基因网络方法对最近发表的数据集进行分析,以确定可能的 COVID-19 炎症机制和生物活性基因。首先,对假定的 SARS-CoV-2 细胞受体进行网络分析,导致挖掘出中性粒细胞反应特征和相关炎症基因。其次,分析感染 SARS-CoV-2 的肺细胞的 RNA-seq 数据集表明,受感染的细胞表达了吸引中性粒细胞的趋化因子。第三,对 COVID-19 患者支气管肺泡灌洗液细胞的 RNA-seq 数据集进行分析,确定了中性粒细胞基因和趋化因子的上调。在这里挖掘出的不同炎症基因,包括 TNFR、IL-8、CXCR1、CXCR2、ADAM10、GPR84、MME、ANPEP 和 LAP3,可能是限制严重临床病例中 SARS-CoV-2 炎症的药物靶点。中性粒细胞在 COVID-19 炎症中的可能作用需要进一步研究。