The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.
The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.
复制标题
感染时肺部的炎症微环境控制着 SARS-CoV-2 复制的先天控制。
DOI：
10.1101/2024.03.27.586885
复制
发表时间：
2024
期刊：
影响因子：
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通讯作者：
Andrade,Brun
中科院分区：
文献类型：
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作者：
Baker,PaulJ;Bohrer,AndreaC;Castro,Ehydel;Amaral,EduardoP;Snow-Smith,Maryonne;Torres-Juárez,Flor;Gould,SydneeT;Queiroz,ArturTL;Fukutani,EduardoR;Jordan,CassandraM;Khillan,JaspalS;Cho,Kyoungin;Barber,DanielL;Andrade,Brun
Severity of COVID-19 is affected by multiple factors; however, it is not understood how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure affects the control of viral replication. Here, we demonstrate that immune events in the mouse lung closely preceding SARS-CoV-2 infection affect viral control and identify innate immune pathways that limit viral replication. Pulmonary inflammatory stimuli including resolved, antecedent respiratory infections withStaphylococcus aureusor influenza, ongoing pulmonaryMycobacterium tuberculosisinfection, ovalbumin/alum-induced asthma, or airway administration of TLR ligands and recombinant cytokines all establish an antiviral state in the lung that restricts SARS-CoV-2 replication. In addition to antiviral type I interferons, TNFα and IL-1 potently precondition the lung for enhanced viral control. Our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation preceding SARS-CoV-2 exposure may contribute to variability in disease outcomes.
