Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
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DOI：
10.1126/science.abc6261
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发表时间：
2020-09-04
期刊：
影响因子：
--
通讯作者：
Pulendran B
中科院分区：
文献类型：
--
作者：
Arunachalam PS;Wimmers F;Mok CKP;Perera RAPM;Scott M;Hagan T;Sigal N;Feng Y;Bristow L;Tak-Yin Tsang O;Wagh D;Coller J;Pellegrini KL;Kazmin D;Alaaeddine G;Leung WS;Chan JMC;Chik TSH;Choi CYC;Huerta C;Paine McCullough M;Lv H;Anderson E;Edupuganti S;Upadhyay AA;Bosinger SE;Maecker HT;Khatri P;Rouphael N;Peiris M;Pulendran B
冠状病毒病2019年(新冠肺炎)已经影响了全球数以百万计的人，但人类免疫系统如何应对和影响新冠肺炎的严重性尚不清楚。Mathew等人。提供了一份与新冠肺炎相关的免疫调节的综合图谱。他们对住院的新冠肺炎患者进行了高维流式细胞术，发现了三种显著且独特的免疫类型，它们与疾病严重程度和临床参数有关。Arunachalam等人。报告了一种系统生物学方法来评估患有轻重病的新冠肺炎患者的免疫系统。这些研究为潜在的治疗干预措施提供了免疫细胞信息和路线图的概要。科学，本期第1210页，新冠肺炎患者的免疫反应被分类，并与健康人的免疫反应进行比较。2019年冠状病毒病(新冠肺炎)是一场全球危机，但关于人类对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的免疫力仍然存在重大知识空白。我们分析了76名新冠肺炎患者和69名来自香港和美国佐治亚州亚特兰大的健康人的免疫反应。在新冠肺炎患者外周血单核细胞中，髓系细胞表达人类白细胞DR类抗原(HLADR)和促炎性细胞因子，浆细胞样树突状细胞(DC)分泌干扰素-α(干扰素-α)和哺乳动物雷帕霉素靶标(MTOR)信号受损。相比之下，我们检测到血浆中炎症介质水平的升高--包括ERAGE、TNFSF14和抑癌素M--它们与疾病严重程度和血浆中细菌产物的增加相关。单细胞转录学显示，重症新冠肺炎患者骨髓细胞中缺乏I型IFN，人类白细胞抗原-DR减少，干扰素刺激基因瞬时表达。这与PBMC大量转录和感染期间血浆中瞬时低水平的干扰素-α一致。这些结果揭示了新冠肺炎的作用机制和潜在的治疗靶点。
Coronavirus disease 2019 (COVID-19) has affected millions of people globally, yet how the human immune system responds to and influences COVID-19 severity remains unclear. Mathew et al. present a comprehensive atlas of immune modulation associated with COVID-19. They performed high-dimensional flow cytometry of hospitalized COVID-19 patients and found three prominent and distinct immunotypes that are related to disease severity and clinical parameters. Arunachalam et al. report a systems biology approach to assess the immune system of COVID-19 patients with mild-to-severe disease. These studies provide a compendium of immune cell information and roadmaps for potential therapeutic interventions. Science, this issue p. , p. 1210 Immune responses of COVID-19 patients are cataloged and compared with those of healthy individuals. Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators—including EN-RAGE, TNFSF14, and oncostatin M—which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.
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