SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs.
SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs.
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SARS-CoV-2 通过促进炎症诱导淋巴细胞减少并摧毁次级淋巴器官
DOI：
10.3389/fimmu.2021.661052
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发表时间：
2021
影响因子：
7.3
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Xiang Q;Feng Z;Diao B;Tu C;Qiao Q;Yang H;Zhang Y;Wang G;Wang H;Wang C;Liu L;Wang C;Liu L;Chen R;Wu Y;Chen Y
虽然淋巴细胞减少症是2019冠状病毒病（COVID-19）的常见特征，但导致这种淋巴细胞耗竭的机制尚不清楚。在此，我们回顾性分析了18例致死性COVID-19病例的临床和免疫学数据，结果显示这些患者存在严重的淋巴细胞减少症，伴血清炎性细胞因子（IL-6、IL-8和IL-10）水平升高，常规实验室检查中许多其他介质升高，包括C-反应蛋白、乳酸脱氢酶、α-羟基丁酸脱氢酶和利钠肽B型。另外6例COVID-19患者的脾脏和肺门淋巴结（LN）也进行了尸检，组织病理学检测显示，这6例患者的脾脏和肺门淋巴结（LN）均表现为严重的组织损伤和淋巴细胞凋亡。原位杂交分析表明，SARS-CoV-2病毒RNA在这些组织中积累，透射电子显微镜证实，冠状病毒样颗粒在淋巴结中可见。SARS-CoV-2刺突蛋白（Spike）和核衣壳蛋白（Nucleocapsidprotein，NP）在脾脏和淋巴结中聚集，NP抗原主要分布于血管紧张素转换酶2（ACE 2）阳性的巨噬细胞和树突状细胞（Dendritic cell，DC）。此外，SARS-CoV-2在体外可激活IL 6、IL 8和IL 1b基因在感染的原代巨噬细胞和DC中的转录，SARS-CoV-2-NP+巨噬细胞和DC也表现出高水平的IL-6和IL-1β，这可能直接杀伤人脾脏和淋巴结，随后导致体内淋巴细胞减少。总的来说，这些结果表明SARS-CoV-2通过促进全身炎症和人脾脏和淋巴结中的直接中和而诱导淋巴细胞减少。
While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6, Il8 and Il1b genes in infected primary macrophages and DCs in vitro, and SARS-CoV-2-NP+ macrophages and DCs also manifested high levels of IL-6 and IL-1β, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.
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影响因子：
5.7
作者：
Komohara Y;Ohnishi K;Takeya M
通讯作者：
Takeya M
影响因子：
9
作者：
Newton AH;Cardani A;Braciale TJ
通讯作者：
Braciale TJ
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影响因子：
15.3
作者：
Gu, Jiang;Gong, Encong;Zhang, Bo;Zheng, Jie;Gao, Zifen;Zhong, Yanfeng;Zou, Wanzhong;Zhan, Jun;Wang, Shenglan;Xie, Zhigang;Zhuang, Hui;Wu, Bingquan;Zhong, Haohao;Shao, Hongquan;Fang, Weigang;Gao, Dongshia;Pei, Fei;Li, Xingwang;He, Zhongpin;Xu, Danzhen;Shi, Xeying;Anderson, Virginia M;Leong, Anthony S-Y
通讯作者：
Leong, Anthony S-Y
影响因子：
5
作者：
Frieman, Matthew;Heise, Mark;Baric, Ralph
通讯作者：
Baric, Ralph
影响因子：
6.4
作者：
Falasca, Laura;Nardacci, Roberta;Del Nonno, Franca
通讯作者：
Del Nonno, Franca