| Author | Baker, Paul J. | |
| Author | Bohrer, Andrea C. | |
| Author | Castro, Ehydel | |
| Author | Amaral, Eduardo P. | |
| Author | Snow-Smith, Maryonne | |
| Author | Torres-Juárez, Flor | |
| Author | Gould, Sydnee T. | |
| Author | Queiroz, Artur T. L. | |
| Author | Fukutani, Eduardo R. | |
| Author | Jordan, Cassandra M. | |
| Author | Khillan, Jaspal S. | |
| Author | Cho, Kyoungin | |
| Author | Barber, Daniel L. | |
| Author | Andrade, Bruno B. | |
| Author | Johnson, Reed F. | |
| Author | Hilligan, Kerry L. | |
| Author | Mayer-Barber, Katrin D. | |
| Access date | 2025-01-21T11:39:10Z | |
| Available date | 2025-01-21T11:39:10Z | |
| Document date | 2024 | |
| 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. | |
| URI | https://www.arca.fiocruz.br/handle/icict/68149 | |
| Sponsorship | Division of Intramural Research. National Institute of Allergy and Infectious Diseases (NIAID). Fundação Oswaldo Cruz, Programa de Pesquisa Intramural. Fundação Civil de Pesquisa e Desenvolvimento (CRDF). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). | |
| Language | eng | en_US |
| Publisher | Cold Spring Harbor | |
| Rights | open access | |
| Subject in Portuguese | Tempo | pt_BR |
| Subject in Portuguese | Pulmão | pt_BR |
| Subject in Portuguese | Infecções | pt_BR |
| Subject in Portuguese | SARS-CoV-2 | pt_BR |
| Title | The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication | en_US |
| Type | Preprint | |
| 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. | en_US |
| 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. | |
| 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. | |
| 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. | |
| 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. | |
| 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 / Centre for Innate Immunity and Infectious Diseases. Hudson Institute of Medical Research. Clayton, Victoria, Australia. | |
| 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. | |
| Affilliation | Human Eosinophil Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA / Malaghan Institute of Medical Research. Wellington, New Zealand. | |
| Affilliation | 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. | |
| Affilliation | 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. | |
| 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. | |
| Affilliation | Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil. | |
| Affilliation | Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil. | |
| Affilliation | Human Eosinophil Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, Maryland, USA. | |
| Affilliation | 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. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional, Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil. | |
| Affilliation | Mouse Genetics and Gene Modification Section. Comparative Medicine Branch. NIAID. NIH. Rockville, Maryland, USA. | |
| 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. | |
| Subject | Time | en_US |
| Subject | Lung | en_US |
| Subject | Infections | en_US |
| Subject | SARS-CoV-2 | en_US |
