The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 27. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Baker, Paul J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 25.04.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2024.03.27.586885 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370752589 |
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| 245 | 1 | 4 | |a The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Bohrer, Andrea C |e verfasserin |4 aut | |
| 700 | 1 | |a Castro, Ehydel |e verfasserin |4 aut | |
| 700 | 1 | |a Amaral, Eduardo P |e verfasserin |4 aut | |
| 700 | 1 | |a Snow-Smith, Maryonne |e verfasserin |4 aut | |
| 700 | 1 | |a Torres-Juárez, Flor |e verfasserin |4 aut | |
| 700 | 1 | |a Gould, Sydnee T |e verfasserin |4 aut | |
| 700 | 1 | |a Queiroz, Artur T L |e verfasserin |4 aut | |
| 700 | 1 | |a Fukutani, Eduardo R |e verfasserin |4 aut | |
| 700 | 1 | |a Jordan, Cassandra M |e verfasserin |4 aut | |
| 700 | 1 | |a Khillan, Jaspal S |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Kyoungin |e verfasserin |4 aut | |
| 700 | 1 | |a Barber, Daniel L |e verfasserin |4 aut | |
| 700 | 1 | |a Andrade, Bruno B |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Reed F |e verfasserin |4 aut | |
| 700 | 1 | |a Hilligan, Kerry L |e verfasserin |4 aut | |
| 700 | 1 | |a Mayer-Barber, Katrin D |e verfasserin |4 aut | |
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