Association of pyroptosis and severeness of COVID-19 as revealed by integrated single-cell transcriptome data analysis.
Association of pyroptosis and severeness of COVID-19 as revealed by integrated single-cell transcriptome data analysis.
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DOI：
10.1016/j.immuno.2022.100013
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发表时间：
2022-06
期刊：
影响因子：
--
通讯作者：
Cai JJ
中科院分区：
文献类型：
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作者：
Xu Q;Yang Y;Zhang X;Cai JJ
细胞因子风暴和炎性细胞因子释放综合征通常与2019冠状病毒病（COVID-19）的严重病例相关。然而，导致COVID-19相关细胞因子风暴发展并加剧炎症反应的因素尚不清楚。在这里，我们综合分析了来自四项涉及中度或重度COVID-19患者的研究的八种不同细胞类型的37，607个免疫细胞的scRNAseq数据。我们的分析表明，裂解，炎症类型的程序性细胞死亡，可能发挥关键作用的SARS-CoV-2诱导的细胞因子风暴。在中度和重度COVID-19患者中，焦亡的关键标志物（如促炎细胞因子基因IL 1B和IL 18）的表达显著高于健康对照。这种模式在巨噬细胞和嗜中性粒细胞中比在适应性免疫细胞如T细胞和B细胞中更明显。此外，巨噬细胞中干扰素-γ（IFN-γ）的缺乏和ninjurin 1（NINJ 1）的过表达可能会加剧全身炎症，如严重的COVID-19患者所示。最后，我们开发了一种评分指标来定量评估单细胞的焦亡状态，并证明了这种焦亡特征评分对scRNAseq数据的使用。综上所述，我们的研究强调了焦亡途径的重要性，并强调了其临床相关性，表明焦亡是一个细胞过程，可以成为COVID-19相关疾病治疗的潜在靶点。
Cytokine storm and inflammatory cytokine release syndrome are often found to be associated with severe instances of the 2019 coronavirus disease (COVID-19). However, factors that contribute to the development of the COVID-19-associated cytokine storm and intensify the hyperinflammatory response are not well known. Here, we integratively analyzed scRNAseq data of 37,607 immune cells of eight different cell types from four studies involving COVID-19 patients in either moderate or severe conditions. Our analysis showed that pyroptosis—a lytic, inflammatory type of programmed cell death—may play a critical role in the SARS-CoV-2-induced cytokine storm. The expression of the key markers of pyroptosis, such as pro-inflammatory cytokine genes IL1B and IL18, is significantly higher in moderate and severe COVID-19 patients than in healthy controls. The pattern is more pronounced in macrophages and neutrophils than in adaptive immune cells such as T cells and B cells. Furthermore, the lack of interferon-gamma (IFN-γ) and overexpression of ninjurin 1 (NINJ1) in macrophages may exacerbate the systemic inflammation, as shown in severe COVID-19 patients. Finally, we developed a scoring metric to quantitatively assess single cell's pyroptotic state and demonstrated the use of this pyroptosis signature score to scRNAseq data. Taken together, our study underscores the importance of the pyroptosis pathway and highlights its clinical relevance, suggesting that pyroptosis is a cellular process that can be a potential target for the treatment of COVID-19 associated diseases.