Identification of Neutrophil-Related Factor LCN2 for Predicting Severity of Patients With Influenza A Virus and SARS-CoV-2 Infection.
Identification of Neutrophil-Related Factor LCN2 for Predicting Severity of Patients With Influenza A Virus and SARS-CoV-2 Infection.
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DOI：
10.3389/fmicb.2022.854172
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发表时间：
2022
影响因子：
5.2
通讯作者：
Cao, Bin
中科院分区：
文献类型：
--
作者：
Huang, Zhisheng;Li, Hui;Liu, Shuai;Jia, Ju;Zheng, Ying;Cao, Bin
流感和COVID-19是呼吸道传染病，具有高传染性和高突变性的特点，对全球健康构成严重威胁。甲型流感病毒（IAV）和SARS-CoV-2感染后，严重者可发展为急性肺损伤。免疫因子在感染和炎症过程中起重要作用。然而，其分子免疫机制仍不清楚。本研究旨在探索重症感染的免疫相关宿主因子和核心生物标志物，为宿主因子治疗提供新的靶点。从Gene Expression Omnibus获得基因表达谱，并使用Seurat R软件包进行单细胞转录组数据处理。利用差异表达基因分析和细胞聚类分析技术，探索核心宿主基因和基因来源细胞。我们进行了基因本体论富集、京都基因和基因组百科全书分析以及基因集富集分析，以探索基因的潜在生物学功能。基因集变异分析用于评估不同样品的重要基因集变异得分。我们采用酶联免疫吸附试验（ELISA）检测血浆脂质运载蛋白2（LCN 2）浓度。在IAV感染和炎症反应过程中涉及多种病毒相关、嘌呤相关和趋化因子相关途径，主要来源于巨噬细胞和中性粒细胞。无论是IAV还是SARS-CoV-2感染后，LCN 2主要在中性粒细胞中显著上调，并与疾病严重程度呈正相关。流感患者血浆LCN 2水平明显高于健康对照组，且与流感患者病情严重程度呈正相关。进一步的生物信息学分析表明，LCN 2参与了中性粒细胞的功能，包括中性粒细胞脱粒，参与免疫反应的中性粒细胞活化，以及中性粒细胞胞外陷阱的形成。LCN 2可能是预测IAV和SARS-CoV-2感染患者病情严重程度的生物标志物，并可能成为重症患者治疗的新靶点。
Influenza and COVID-19 are respiratory infectious diseases that are characterized by high contagiousness and high mutation and pose a serious threat to global health. After Influenza A virus (IAV) and SARS-CoV-2 infection, severe cases may develop into acute lung injury. Immune factors act as an important role during infection and inflammation. However, the molecular immune mechanisms still remain unclear. We aimed to explore immune-related host factors and core biomarker for severe infection, to provide a new therapeutic target of host factor in patients. Gene expression profiles were obtained from Gene Expression Omnibus and the Seurat R package was used for data process of single-cell transcriptome. Differentially expressed gene analysis and cell cluster were used to explore core host genes and source cells of genes. We performed Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis to explore potential biological functions of genes. Gene set variation analysis was used to evaluate the important gene set variation score for different samples. We conduct Enzyme-linked immunosorbent assay (ELISA) to test plasma concentrations of Lipocalin 2 (LCN2). Multiple virus-related, cytokine-related, and chemokine-related pathways involved in process of IAV infection and inflammatory response mainly derive from macrophages and neutrophils. LCN2 mainly in neutrophils was significantly upregulated after either IAV or SARS-CoV-2 infection and positively correlated with disease severity. The plasma LCN2 of influenza patients were elevated significantly compared with healthy controls by ELISA and positively correlated with disease severity of influenza patients. Further bioinformatics analysis revealed that LCN2 involved in functions of neutrophils, including neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil extracellular trap formation. The neutrophil-related LCN2 could be a promising biomarker for predicting severity of patients with IAV and SARS-CoV-2 infection and may as a new treatment target in severe patients.
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作者：
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DOI：
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影响因子：
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DOI：
10.1093/rheumatology/keaa368
发表时间：
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期刊：
Rheumatology (Oxford, England)
影响因子：
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通讯作者：
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