先天免疫系统
免疫系统
免疫学
炎症
细胞因子
医学
病毒载量
促炎细胞因子
干扰素基因刺激剂
细胞激素风暴
Ⅰ型干扰素
TLR7型
作者
Esen Sefik,Rihao Qu,Eleanna Kaffe,Jun Zhao,Haris Mirza,Ricky Brewer,Ailin Han,Holly R. Steach,Benjamin Israelow,Y. Grace Chen,Stephanie Halene,Akiko Iwasaki,Eric Meffre,Michel C. Nussenzweig,Craig B. Wilen,Yuval Kluger,Richard A. Flavell
标识
DOI:10.1101/2021.09.27.461948
摘要
Chronic COVID-19 is characterized by persistent viral RNA and sustained interferon (IFN) response which is recapitulated and required for pathology in SARS-CoV-2 infected MISTRG6-hACE2 humanized mice. As in the human disease, monocytes, and macrophages in SARS-CoV-2 infected MISTRG6-hACE2 are central to disease pathology. Here, we describe SARS-CoV-2 uptake in tissue resident human macrophages that is enhanced by virus specific antibodies. SARS-CoV-2 replicates in these human macrophages as evidenced by detection of double-stranded RNA, subgenomic viral RNA and expression of a virally encoded fluorescent reporter gene; and it is inhibited by Remdesivir, an inhibitor of viral replication. Although early IFN deficiency leads to enhanced disease, blocking either viral replication with Remdesivir or the downstream IFN stimulated cascade by injecting anti-IFNAR2 in vivo in the chronic stages of disease attenuates many aspects of the overactive immune-inflammatory response, especially the inflammatory macrophage response, and most consequentially, the chronic disease itself.
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