dc.contributor.author
Högner, Katrin
dc.contributor.author
Wolff, Thorsten
dc.contributor.author
Pleschka, Stephan
dc.contributor.author
Plog, Stephanie
dc.contributor.author
Gruber, Achim D.
dc.contributor.author
Kalinke, Ulrich
dc.contributor.author
Walmrath, Hans-Dieter
dc.contributor.author
Bodner, Johannes
dc.contributor.author
Gattenlöhner, Stefan
dc.contributor.author
Lewe-Schlosser, Peter
dc.contributor.author
Matrosovich, Mikhail
dc.contributor.author
Seeger, Werner
dc.contributor.author
Lohmeyer, Juergen
dc.contributor.author
Herold, Susanne
dc.date.accessioned
2018-06-08T04:16:13Z
dc.date.available
2014-01-26T17:45:22.018Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/16941
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-21122
dc.description.abstract
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.
de
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/deed.de
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::630 Landwirtschaft
dc.title
Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell
injury in severe influenza virus pneumonia
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS Pathogens; Febr. 2013,9 (2), e1003188
dcterms.bibliographicCitation.doi
10.1371/journal.ppat.1003188
dcterms.bibliographicCitation.url
http://dx.doi.org/10.1371/journal.ppat.1003188
refubium.affiliation
Veterinärmedizin
de
refubium.affiliation.other
Institut für Tierpathologie
refubium.mycore.fudocsId
FUDOCS_document_000000019489
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000002957
dcterms.accessRights.openaire
open access