Baker Paul J, Bohrer Andrea C, Castro Ehydel, Amaral Eduardo P, Snow-Smith Maryonne, Torres-Juárez Flor, Gould Sydnee T, Queiroz Artur T L, Fukutani Eduardo R, Jordan Cassandra M, Khillan Jaspal S, Cho Kyoungin, Barber Daniel L, Andrade Bruno B, Johnson Reed F, Hilligan Kerry L, Mayer-Barber Katrin D
Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Human Eosinophil Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
Sci Immunol. 2024 Dec 6;9(102):eadp7951. doi: 10.1126/sciimmunol.adp7951.
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 with or influenza, ongoing pulmonary infection, 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.
新冠病毒肺炎（COVID-19）的严重程度受多种因素影响；然而，目前尚不清楚严重急性呼吸综合征冠状病毒2（SARS-CoV-2）暴露时肺部的炎症环境如何影响病毒复制的控制。在此，我们证明在SARS-CoV-2感染之前小鼠肺部的免疫事件会影响病毒控制，并确定了限制病毒复制的固有免疫途径。肺部炎症刺激，包括已痊愈的既往呼吸道感染（如流感）、正在进行的肺部感染、卵清蛋白/明矾诱导的哮喘，或经气道给予Toll样受体（TLR）配体和重组细胞因子，均可在肺部建立抗病毒状态，从而限制SARS-CoV-2复制。除了抗病毒I型干扰素外，肿瘤坏死因子α（TNFα）和白细胞介素-1（IL-1）也能有效地使肺部预先具备更强的病毒控制能力。我们的研究表明，SARS-CoV-2可能受益于免疫静止的肺部微环境，并提示SARS-CoV-2暴露之前肺部炎症的异质性可能导致疾病结局的差异。
