| First Author | Schneider C | Year | 2014 |
| Journal | PLoS Pathog | Volume | 10 |
| Issue | 4 | Pages | e1004053 |
| PubMed ID | 24699679 | Mgi Jnum | J:245844 |
| Mgi Id | MGI:5916170 | Doi | 10.1371/journal.ppat.1004053 |
| Citation | Schneider C, et al. (2014) Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. PLoS Pathog 10(4):e1004053 |
| abstractText | 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 CD8alpha+ 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. |
