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COVID-19严重程度与气道上皮与免疫细胞相互作用有关
2020-06-30 17:34

德国柏林大学Roland Eils等研究人员合作利用单细胞分析发现,COVID-19严重程度与气道上皮与免疫细胞相互作用有关。相关论文于2020年6月26日在线发表在《自然—生物技术》杂志上。

为了研究与2019严重冠状病毒病(COVID-19)相关的免疫应答和机制,研究人员对19名临床特征明确的中度或重症患者以及五个健康对照的鼻咽和支气管样本进行了单细胞RNA测序。研究人员确定了易受严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)感染的气道上皮细胞的类型和状态。在患有COVID-19的病人中,上皮细胞的SARS-CoV-2受体ACE2的表达平均增加了三倍,这与免疫细胞的干扰素信号相关。
 
与中度病例相比,危重病例表现出的上皮细胞与免疫细胞之间的相互作用更强,比如配体-受体表达谱和活化的免疫细胞,这其中包括表达CCL2、CCL3、CCL20、CXCL1、CXCL3、CXCL10、IL8、IL1B以TNF的炎性巨噬细胞。
 
与中度病例相比,危重病例的转录差异可能促进了临床观察到炎性组织损伤、肺损伤和呼吸衰竭加剧。这些数据表明,CCR1和/或CCR5途径的药理抑制作用可能会抑制重症COVID-19中的免疫过度活化。
 
附:英文原文

Title: COVID-19 severity correlates with airway epithelium–immune cell interactions identified by single-cell analysis

Author: Robert Lorenz Chua, Soeren Lukassen, Saskia Trump, Bianca P. Hennig, Daniel Wendisch, Fabian Pott, Olivia Debnath, Loreen Thrmann, Florian Kurth, Maria Theresa Vlker, Julia Kazmierski, Bernd Timmermann, Sven Twardziok, Stefan Schneider, Felix Machleidt, Holger Mller-Redetzky, Melanie Maier, Alexander Krannich, Sein Schmidt, Felix Balzer, Johannes Liebig, Jennifer Loske, Norbert Suttorp, Jrgen Eils, Naveed Ishaque, Uwe Gerd Liebert, Christof von Kalle, Andreas Hocke, Martin Witzenrath, Christine Goffinet, Christian Drosten, Sven Laudi, Irina Lehmann, Christian Conrad, Leif-Erik Sander, Roland Eils

Issue&Volume: 2020-06-26

Abstract: To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.

DOI: 10.1038/s41587-020-0602-4

Source: https://www.nature.com/articles/s41587-020-0602-4

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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