Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer
Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer
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DOI：
10.1016/j.jinf.2020.07.016
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发表时间：
2020-10-01
影响因子：
28.2
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
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作者：
Shuai, Huiping;Chu, Hin;Yuen, Kwok-Yung
目的：呼吸道和肠道是SARS-CoV-2感染的两个主要靶器官。方法：以人肺(Calu3)和肠(Caco 2)上皮细胞为研究对象，采用免疫荧光分析、流式细胞术和RT-qPCR等方法，对SARS-CoV-2感染的人肺上皮细胞和肠道上皮细胞的病毒特性和宿主细胞的天然免疫应答进行了研究。结果：肺上皮细胞对SARS-CoV-2的敏感性明显高于SARS-CoV。然而，SARS-CoV-2感染诱导的促炎细胞因子/趋化因子诱导以及I型和II型干扰素应答减弱。单次注射10U/mLβ干扰素可有效地保护CALU3和CACO2免受SARS-CoV-2感染。有趣的是，SARS-CoV-2对干扰素β和干扰素诱导剂的预处理比SARS-CoV-3更敏感。结论：尽管SARS-CoV-2在人肺和肠上皮细胞中均有强烈感染，但SARS-CoV-2可减弱病毒诱导的促炎反应和干扰素应答。I型干扰素信号通路的预激活在宿主体内启动了针对SARS-CoV-2感染的高效抗病毒反应，这可能是一种潜在的新冠肺炎患者的治疗和预防策略。(C)2020年英国感染协会。爱思唯尔有限公司出版。保留所有权利。
Objectives: Respiratory and intestinal tract are two primary target organs of SARS-CoV-2 infection. How-ever, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking.Methods: We utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the viro-logical features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human lung (Calu3) and intestinal (Caco2) epithelium when compared with SARS-CoV.Results: Lung epithelial cells were significantly more susceptible to SARS-CoV-2 compared to SARS-CoV. However, SARS-CoV-2 infection induced an attenuated pro-inflammatory cytokines/chemokines induction and type I and type II IFN responses. A single dose of 10 U/mL interferon-beta (IFN beta) pretreatment potently protected both Calu3 and Caco2 against SARS-CoV-2 infection. Interestingly, SARS-CoV-2 was more sensitive to the pretreatment with IFN beta and IFN inducer than SARS-CoV in Calu3.Conclusions: Despite robust infection in both human lung and intestinal epithelial cells, SARS-CoV-2 could attenuate the virus-induced pro-inflammatory response and IFN response. Pre-activation of the type I IFN signaling pathway primed a highly efficient antiviral response in the host against SARS-CoV-2 infection, which could serve as a potential therapeutic and prophylactic maneuver to COVID-19 patients. (C) 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.