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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
SCV2 Virology Core. Laboratory of Viral 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.
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 / Centre for Innate Immunity and Infectious Diseases. Hudson Institute of Medical Research. Clayton, Victoria, Australia.
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 / Malaghan Institute of Medical Research. Wellington, New Zealand.
T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA / Department of Molecular and Cell Biology. University of California. Berkeley, CA, USA.
T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA / Department of Molecular and Cell Biology. University of California. Berkeley, CA, 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.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
Human Eosinophil Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA.
T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA / Department of Molecular and Cell Biology. University of California. Berkeley, CA, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional, Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil.
Mouse Genetics and Gene Modification Section. Comparative Medicine Branch. NIAID. NIH. Rockville, 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.
Abstract
SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with S. aureus or influenza, ongoing pulmonary M. tuberculosis infection, ovalbumin/alum-induced asthma or airway administration of defined TLR ligands and recombinant cytokines, all establish an antiviral state in the lung that restricts SARS-CoV-2 replication upon infection. In addition to antiviral type I interferons, the broadly inducible inflammatory cytokines TNFα and IL-1 precondition the lung for enhanced viral control. Collectively, our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation that precedes or accompanies SARS-CoV-2 exposure may be a significant factor contributing to the population-wide variability in COVID-19 disease outcomes.
Keywords in Portuguese
Tempo
Pulmão
Infecções
SARS-CoV-2
 
Keywords
Time
Lung
Infections
SARS-CoV-2
 
Publisher
Cold Spring Harbor
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. BioRxiv, p. 1-59, 2024.