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Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection.

  • Schneider C Molecular Biomedicine, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland.
  • Nobs SP Molecular Biomedicine, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland.
  • Heer AK Molecular Biomedicine, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland.
  • Kurrer M Pathology Institute, Zurich, Switzerland.
  • Klinke G Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
  • van Rooijen N Department of Molecular Cell Biology, Free University Medical Center, Amsterdam, The Netherlands.
  • Vogel J Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland.
  • Kopf M Molecular Biomedicine, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland.
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  • 2014-04-05
Published in:
  • PLoS pathogens. - 2014
Animals
CD8-Positive T-Lymphocytes
Cytokine Receptor Common beta Subunit
Dendritic Cells
Immunity, Cellular
Influenza A Virus, H1N1 Subtype
Macrophages, Alveolar
Mice
Mice, Knockout
Orthomyxoviridae Infections
PPAR gamma
Respiratory Insufficiency
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.rero.ch/global/documents/277572
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