PLoS Pathogens | |
Alveolar Macrophages Are Essential for Protection from Respiratory Failure and Associated Morbidity following Influenza Virus Infection | |
Nico van Rooijen1  Glynis Klinke2  Johannes Vogel3  Christoph Schneider4  Alex K. Heer4  Manfred Kopf4  Samuel P. Nobs4  Michael Kurrer5  | |
[1] Department of Molecular Cell Biology, Free University Medical Center, Amsterdam, The Netherlands;Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland;Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland;Molecular Biomedicine, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland;Pathology Institute, Zurich, Switzerland | |
关键词: Respiratory infections; Influenza viruses; T cells; Morbidity; Cytotoxic T cells; Influenza; Alveolar macrophages; Viral transmission; infection; | |
DOI : 10.1371/journal.ppat.1004053 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201902010247935ZK.pdf | 2537KB | download |