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THE INFLAMMATORY MICROENVIRONMENT OF THE LUNG AT THE TIME OF INFECTION GOVERNS INNATE CONTROL OF SARS-COV- 2 REPLICATION
Baker, Paul J. et al. | Date Issued: 2024
Author
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.
Affilliation
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, Maryland, USA.
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, Maryland, USA.
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, Maryland, USA.
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, Maryland, USA.
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, Maryland, USA / Human Eosinophil Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA.
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, Maryland, USA.
T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional, Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional, Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil.
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, Maryland, USA.
Mouse Genetics and Gene Modification Section. Comparative Medicine Branch. NIAID. NIH. Rockville, Maryland, USA.
Mouse Genetics and Gene Modification Section. Comparative Medicine Branch. NIAID. NIH. Rockville, Maryland, USA.
T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional, Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil.
SCV2 Virology Core. Laboratory of Viral Diseases. NIAID. NIH. Bethesda, Maryland, USA.
Malaghan Institute of Medical Research. Wellington, New Zealand.
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, Maryland, USA.
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.
Keywords
Time
Lung
Infections
SARS-CoV-2
 
Publisher
American Association for the Advancement of Science
Citation
BAKER, Paul J. et al. The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication. Sci. Immunol. v. 9, n. 102, p. 1-18, 2024.
DOI
10.1126/sciimmunol.adp7951
ISSN
2470-9468