The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication
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 <i>Staphylococcus aureus</i> or influenza, ongoing pulmonary <i>Mycobacterium tuberculosis</i> 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.
Authors
- Bruno B. Andrade (ORCID: https://orcid.org/0000-0001-6833-3811)
- Kerry L. Hilligan (ORCID: https://orcid.org/0000-0003-1238-1552)
- Andrea C. Bohrer
- Sydnee T. Gould
- Maryonne Snow-Smith
- Paul J. Baker (ORCID: https://orcid.org/0000-0002-3642-2366)
- Ehydel Castro (ORCID: https://orcid.org/0000-0001-5900-248X)
- Eduardo P. Amaral (ORCID: https://orcid.org/0000-0001-5465-8113)
- Daniel L. Barber (ORCID: https://orcid.org/0000-0001-7008-7509)
- Artur T. L. Queiroz (ORCID: https://orcid.org/0000-0003-4908-9993)
- Cassandra M. Jordan
- Reed F. Johnson (ORCID: https://orcid.org/0000-0002-4312-0550)
- Kyoungin Cho
- Eduardo R. Fukutani (ORCID: https://orcid.org/0000-0001-6326-8731)
- Jaspal S. Khillan (ORCID: https://orcid.org/0000-0003-2169-9159)
- Katrin D. Mayer-Barber
- Flor Torres-Juárez (ORCID: https://orcid.org/0000-0003-4526-4678)
Institutions
- National Institutes of Health (US)
- Malaghan Institute of Medical Research (NZ)
- Jiangsu Institute of Parasitic Diseases (CN)
- Department of Virology (FR)
- National Institute of Allergy and Infectious Diseases (US)
- Ministry of Health (TT)
- Fundação Oswaldo Cruz (BR)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-12-06
- DOI
- https://doi.org/10.1126/sciimmunol.adp7951
- Citations
- 8
- Primary Topic
- COVID-19 Clinical Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 3.11