Alveolar Macrophages Are Essential for Protection from Respiratory Failure and Associated Morbidity following Influenza Virus Infection

PLoS Pathogens

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