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2013-02-28Zeitschriftenartikel DOI: 10.1371/journal.ppat.1003188
Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia
dc.contributor.authorHögner, Katrin
dc.contributor.authorWolff, Thorsten
dc.contributor.authorPleschka, Stephan
dc.contributor.authorPlog, Stephanie
dc.contributor.authorGruber, Achim D.
dc.contributor.authorKalinke, Ulrich
dc.contributor.authorWalmrath, Hans-Dieter
dc.contributor.authorBodner, Johannes
dc.contributor.authorGattenlöhner, Stefan
dc.contributor.authorLewe-Schlosser, Peter
dc.contributor.authorMatrosovich, Mikhail
dc.contributor.authorSeeger, Werner
dc.contributor.authorLohmeyer, Jürgen
dc.contributor.authorHerold, Susanne
dc.date.accessioned2018-05-07T16:19:54Z
dc.date.available2018-05-07T16:19:54Z
dc.date.created2013-03-27
dc.date.issued2013-02-28none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/renJsw2fERg/PDF/26ZYhM1HjyzsM.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1438
dc.description.abstractInfluenza 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.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subjectAnimalseng
dc.subjectHumanseng
dc.subjectAdulteng
dc.subjectMiceeng
dc.subjectAcute Lung Injury/immunologyeng
dc.subjectAcute Lung Injury/metabolismeng
dc.subjectAcute Lung Injury/pathologyeng
dc.subjectApoptosiseng
dc.subjectDisease Models Animaleng
dc.subjectInfluenza Human/immunologyeng
dc.subjectInfluenza Human/metabolismeng
dc.subjectInfluenza Human/pathologyeng
dc.subjectInterferon-beta/metabolismeng
dc.subjectMacrophages Alveolar/immunologyeng
dc.subjectMacrophages Alveolar/metabolismeng
dc.subjectMacrophages Alveolar/pathologyeng
dc.subjectMice Inbred C57BLeng
dc.subjectMice Knockouteng
dc.subjectMice Transgeniceng
dc.subjectMosaicismeng
dc.subjectPneumonia Viral/immunologyeng
dc.subjectPneumonia Viral/metabolismeng
dc.subjectPneumonia Viral/pathologyeng
dc.subjectRespiratory Mucosa/immunologyeng
dc.subjectRespiratory Mucosa/metabolismeng
dc.subjectRespiratory Mucosa/pathologyeng
dc.subjectTNF-Related Apoptosis-Inducing Ligand/metabolismeng
dc.subject.ddc610 Medizin
dc.titleMacrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10029827
dc.identifier.doi10.1371/journal.ppat.1003188
dc.identifier.doihttp://dx.doi.org/10.25646/1363
local.edoc.container-titlePLoS Pathogens
local.edoc.container-textHögner K, Wolff T, Pleschka S, Plog S, Gruber AD, et al. (2013) Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia. PLoS Pathog 9(2): e1003188.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003188
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume9
local.edoc.container-issue2
local.edoc.container-year2013

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