叙利亚仓鼠的时间组学分析揭示了细胞对中度 COVID-19 的效应反应,Nature Communications

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叙利亚仓鼠的时间组学分析揭示了细胞对中度 COVID-19 的效应反应
Nature Communications ( IF 14.7 ) Pub Date : 2021-08-11 , DOI: 10.1038/s41467-021-25030-7
Geraldine Nouailles _{1,

2} , Emanuel Wyler ₃ , Peter Pennitz ₁ , Dylan Postmus _{2,

4} , Daria Vladimirova ₅ , Julia Kazmierski _{2,

4} , Fabian Pott _{2,

4} , Kristina Dietert _{6,

7} , Michael Muelleder ₈ , Vadim Farztdinov ₈ , Benedikt Obermayer ₉ , Sandra-Maria Wienhold ₁ , Sandro Andreotti ₁₀ , Thomas Hoefler ₅ , Birgit Sawitzki ₁₁ , Christian Drosten ₄ , Leif E Sander ₁₂ , Norbert Suttorp ₁₂ , Markus Ralser _{13,

14} , Dieter Beule ₉ , Achim D Gruber ₆ , Christine Goffinet _{2,

4} , Markus Landthaler _{3,

15} , Jakob Trimpert ₅ , Martin Witzenrath _{1,

12,

16}

Affiliation

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany.
Berlin Institute of Health (BIH), Berlin, Germany.
Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany.
Institute of Virology, Freie Universität Berlin, Berlin, Germany.
Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
Veterinary Centre for Resistance Research, Freie Universität Berlin, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Core Facility - High-Throughput Mass Spectrometry, Berlin, Germany.
Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics, Berlin, Germany.
Bioinformatics Solution Center, Freie Universität Berlin, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Immunology, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany.
The Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, UK.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Biochemistry, Berlin, Germany.
IRI Life Sciences, Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
German Center for Lung Research (DZL), Berlin, Germany.

在 COVID-19 中，免疫反应是确定疾病严重程度的关键。然而，SARS-CoV-2 感染中炎症性肺损伤发生的细胞机制，特别是涉及内皮细胞的细胞机制，仍然不明确。我们使用叙利亚仓鼠作为中度 COVID-19 的模型，对全身和肺部细胞反应进行了详细的纵向分析，并用来自 COVID-19 患者的数据集进行了证实。肺部的单核细胞衍生的巨噬细胞对感染发挥最早、最强的转录反应，包括诱导促炎基因，而上皮细胞则表现出微弱的改变。如果没有有效感染的证据，内皮细胞会根据细胞亚型，通过抗病毒、促炎和 T 细胞募集基因的强烈和早期表达来做出反应。感染后第 5 天，细胞毒性 T 细胞的募集以及 IgM 抗体的出现先于病毒清除。通过研究 SARS-CoV-2 感染的叙利亚仓鼠，可以识别细胞类型特异性效应器功能，从而详细了解 COVID-19 的病理机制并为治疗策略提供信息。

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更新日期：2021-08-11

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