The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

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  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Association for the Advancement of Science, [2016]-
    • Subject Terms:
      SARS-CoV-2*/immunology ; COVID-19*/immunology ; Virus Replication*/immunology ; Lung*/immunology ; Lung*/virology ; Immunity, Innate*/immunology; Animals ; Mice ; Mice, Inbred C57BL ; Humans ; Female ; Inflammation/immunology
    • Abstract:
      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 Staphylococcus aureus or influenza, ongoing pulmonary Mycobacterium tuberculosis 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.
    • Comments:
      Update of: bioRxiv. 2024 Mar 27:2024.03.27.586885. doi: 10.1101/2024.03.27.586885. (PMID: 38585846)
    • Publication Date:
      Date Created: 20241206 Date Completed: 20241206 Latest Revision: 20241210
    • Publication Date:
      20241210
    • Accession Number:
      10.1126/sciimmunol.adp7951
    • Accession Number:
      39642242