Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection.
Alveolar macrophages (AM) are critical for defense against bacterial and fungal infections. However, a definitive role of AM in viral infections remains unclear. We here report that AM play a key role in survival to influenza and vaccinia virus infection by maintaining lung function and thereby prot...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-04-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004053&type=printable |
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| author | Christoph Schneider Samuel P Nobs Alex K Heer Michael Kurrer Glynis Klinke Nico van Rooijen Johannes Vogel Manfred Kopf |
| author_facet | Christoph Schneider Samuel P Nobs Alex K Heer Michael Kurrer Glynis Klinke Nico van Rooijen Johannes Vogel Manfred Kopf |
| author_sort | Christoph Schneider |
| collection | DOAJ |
| description | Alveolar macrophages (AM) are critical for defense against bacterial and fungal infections. However, a definitive role of AM in viral infections remains unclear. We here report that AM play a key role in survival to influenza and vaccinia virus infection by maintaining lung function and thereby protecting from asphyxiation. Absence of AM in GM-CSF-deficient (Csf2-/-) mice or selective AM depletion in wild-type mice resulted in impaired gas exchange and fatal hypoxia associated with severe morbidity to influenza virus infection, while viral clearance was affected moderately. Virus-induced morbidity was far more severe in Csf2-/- mice lacking AM, as compared to Batf3-deficient mice lacking CD8α+ and CD103+ DCs. Csf2-/- mice showed intact anti-viral CD8+ T cell responses despite slightly impaired CD103+ DC development. Importantly, selective reconstitution of AM development in Csf2rb-/- mice by neonatal transfer of wild-type AM progenitors prevented severe morbidity and mortality, demonstrating that absence of AM alone is responsible for disease severity in mice lacking GM-CSF or its receptor. In addition, CD11c-Cre/Ppargfl/fl mice with a defect in AM but normal adaptive immunity showed increased morbidity and lung failure to influenza virus. Taken together, our results suggest a superior role of AM compared to CD103+ DCs in protection from acute influenza and vaccinia virus infection-induced morbidity and mortality. |
| format | Article |
| id | doaj-art-b4192f1e80484aab8aeb96182700bffb |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2014-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-b4192f1e80484aab8aeb96182700bffb2025-08-20T03:00:25ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-04-01104e100405310.1371/journal.ppat.1004053Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection.Christoph SchneiderSamuel P NobsAlex K HeerMichael KurrerGlynis KlinkeNico van RooijenJohannes VogelManfred KopfAlveolar macrophages (AM) are critical for defense against bacterial and fungal infections. However, a definitive role of AM in viral infections remains unclear. We here report that AM play a key role in survival to influenza and vaccinia virus infection by maintaining lung function and thereby protecting from asphyxiation. Absence of AM in GM-CSF-deficient (Csf2-/-) mice or selective AM depletion in wild-type mice resulted in impaired gas exchange and fatal hypoxia associated with severe morbidity to influenza virus infection, while viral clearance was affected moderately. Virus-induced morbidity was far more severe in Csf2-/- mice lacking AM, as compared to Batf3-deficient mice lacking CD8α+ and CD103+ DCs. Csf2-/- mice showed intact anti-viral CD8+ T cell responses despite slightly impaired CD103+ DC development. Importantly, selective reconstitution of AM development in Csf2rb-/- mice by neonatal transfer of wild-type AM progenitors prevented severe morbidity and mortality, demonstrating that absence of AM alone is responsible for disease severity in mice lacking GM-CSF or its receptor. In addition, CD11c-Cre/Ppargfl/fl mice with a defect in AM but normal adaptive immunity showed increased morbidity and lung failure to influenza virus. Taken together, our results suggest a superior role of AM compared to CD103+ DCs in protection from acute influenza and vaccinia virus infection-induced morbidity and mortality.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004053&type=printable |
| spellingShingle | Christoph Schneider Samuel P Nobs Alex K Heer Michael Kurrer Glynis Klinke Nico van Rooijen Johannes Vogel Manfred Kopf Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. PLoS Pathogens |
| title | Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. |
| title_full | Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. |
| title_fullStr | Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. |
| title_full_unstemmed | Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. |
| title_short | Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. |
| title_sort | alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004053&type=printable |
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