Cell-Type-Specific Immune Dysregulation in Severely Ill COVID-19 Patients.
Cell-Type-Specific Immune Dysregulation in Severely Ill COVID-19 Patients.
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严重疾病患者的细胞型特异性免疫失调。
DOI：
10.1016/j.celrep.2020.108590
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发表时间：
2021-01-05
期刊：
影响因子：
8.8
通讯作者：
Chen P
中科院分区：
文献类型：
--
作者：
Yao C;Bora SA;Parimon T;Zaman T;Friedman OA;Palatinus JA;Surapaneni NS;Matusov YP;Cerro Chiang G;Kassar AG;Patel N;Green CER;Aziz AW;Suri H;Suda J;Lopez AA;Martins GA;Stripp BR;Gharib SA;Goodridge HS;Chen P
最近的研究表明，2019 年冠状病毒病 (COVID-19) 重症患者存在免疫功能障碍。我们使用单细胞 RNA 测序 (scRNA-seq) 来分析健康 (n = 3) 和患有中度疾病 (n = 5)、急性呼吸窘迫综合征 (ARDS，n = 6) 或从 ARDS 中恢复的 COVID-19 患者 (n = 6) 的外周血单核细胞 (PBMC) 的转录组。我们的数据揭示了转录组图谱，表明 ARDS 患者的单核细胞中存在缺陷的抗原呈递和干扰素 (IFN) 反应性，这与淋巴细胞中对 IFN 信号传导的较高反应性形成鲜明对比。此外，自然杀伤 (NK) 和 CD8 T 淋巴细胞中涉及细胞毒活性的基因均受到抑制，并且 B 细胞活化不足，这与重症 COVID-19 患者的病毒清除延迟一致。我们的研究表明，患有 ARDS 的 COVID-19 患者处于免疫失衡状态，先天性和适应性免疫反应的失调可能会导致更严重的病程。姚等人。证据表明，患有急性呼吸窘迫综合征的 COVID-19 患者中广泛的、细胞特异性的免疫反应失调可能是疾病严重程度的基础。缺陷包括抗原呈递途径受损、单核细胞对早期抗病毒干扰素信号的反应受到抑制、细胞毒性基因的淋巴细胞表达缺陷以及 B 细胞活化减少。
Recent studies have demonstrated immunologic dysfunction in severely ill coronavirus disease 2019 (COVID-19) patients. We use single-cell RNA sequencing (scRNA-seq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMCs) from healthy (n = 3) and COVID-19 patients with moderate disease (n = 5), acute respiratory distress syndrome (ARDS, n = 6), or recovering from ARDS (n = 6). Our data reveal transcriptomic profiles indicative of defective antigen presentation and interferon (IFN) responsiveness in monocytes from ARDS patients, which contrasts with higher responsiveness to IFN signaling in lymphocytes. Furthermore, genes involved in cytotoxic activity are suppressed in both natural killer (NK) and CD8 T lymphocytes, and B cell activation is deficient, which is consistent with delayed viral clearance in severely ill COVID-19 patients. Our study demonstrates that COVID-19 patients with ARDS have a state of immune imbalance in which dysregulation of both innate and adaptive immune responses may be contributing to a more severe disease course. Yao et al. provide evidence that widespread, cell-specific dysregulation of immune responses in COVID-19 patients with acute respiratory distress syndrome may underlie disease severity. Defects include impaired antigen presentation pathways, suppressed monocyte response to early antiviral interferon signals, deficient lymphocyte expression of cytotoxicity genes, and reduced B cell activation.
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影响因子：
30.5
作者：
Chiu C;Openshaw PJ
通讯作者：
Openshaw PJ
影响因子：
5.4
作者：
Budayeva, Hanna G.;Rowland, Elizabeth A.;Cristea, Ileana M.
通讯作者：
Cristea, Ileana M.
DOI：
10.1016/j.jaip.2020.06.015
发表时间：
2020-09-01
影响因子：
9.4
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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5.4
作者：
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通讯作者：
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