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    Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia (2013)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Högner, Katrin
    Wolff, Thorsten
    Pleschka, Stephan
    Plog, Stephanie (WE 12)
    Gruber, Achim D (WE 12)
    Kalinke, Ulrich
    Walmrath, Hans-Dieter
    Bodner, Johannes
    Gattenlöhner, Stefan
    Lewe-Schlosser, Peter
    Matrosovich, Mikhail
    Seeger, Werner
    Lohmeyer, Juergen
    Herold, Susanne
    Quelle
    PLoS Pathogens; 9(2) — S. e1003188
    ISSN: 1553-7366
    Sprache
    Englisch
    Verweise
    URL (Volltext): http://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000019489
    DOI: 10.1371/journal.ppat.1003188
    Pubmed: 23468627
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    Abstract / Zusammenfassung

    Influenza viruses (IV) cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs) has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM)-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC) injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL). Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR-) and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.