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

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 i...

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Autores principales:	Katrin Högner, Thorsten Wolff, Stephan Pleschka, Stephanie Plog, Achim D Gruber, Ulrich Kalinke, Hans-Dieter Walmrath, Johannes Bodner, Stefan Gattenlöhner, Peter Lewe-Schlosser, Mikhail Matrosovich, Werner Seeger, Juergen Lohmeyer, Susanne Herold
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/16f63be53e5a4d9595813eb57f371aaa
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spelling	oai:doaj.org-article:16f63be53e5a4d9595813eb57f371aaa2021-11-18T06:05:59ZMacrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.1553-73661553-737410.1371/journal.ppat.1003188https://doaj.org/article/16f63be53e5a4d9595813eb57f371aaa2013-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23468627/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Influenza 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.Katrin HögnerThorsten WolffStephan PleschkaStephanie PlogAchim D GruberUlrich KalinkeHans-Dieter WalmrathJohannes BodnerStefan GattenlöhnerPeter Lewe-SchlosserMikhail MatrosovichWerner SeegerJuergen LohmeyerSusanne HeroldPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 2, p e1003188 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Katrin Högner Thorsten Wolff Stephan Pleschka Stephanie Plog Achim D Gruber Ulrich Kalinke Hans-Dieter Walmrath Johannes Bodner Stefan Gattenlöhner Peter Lewe-Schlosser Mikhail Matrosovich Werner Seeger Juergen Lohmeyer Susanne Herold Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.
description	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.
format	article
author	Katrin Högner Thorsten Wolff Stephan Pleschka Stephanie Plog Achim D Gruber Ulrich Kalinke Hans-Dieter Walmrath Johannes Bodner Stefan Gattenlöhner Peter Lewe-Schlosser Mikhail Matrosovich Werner Seeger Juergen Lohmeyer Susanne Herold
author_facet	Katrin Högner Thorsten Wolff Stephan Pleschka Stephanie Plog Achim D Gruber Ulrich Kalinke Hans-Dieter Walmrath Johannes Bodner Stefan Gattenlöhner Peter Lewe-Schlosser Mikhail Matrosovich Werner Seeger Juergen Lohmeyer Susanne Herold
author_sort	Katrin Högner
title	Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.
title_short	Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.
title_full	Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.
title_fullStr	Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.
title_full_unstemmed	Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.
title_sort	macrophage-expressed ifn-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/16f63be53e5a4d9595813eb57f371aaa
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Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.

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