Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice.
dc.contributor.author | Maier, Barbara B | |
dc.contributor.author | Hladik, Anastasiya | |
dc.contributor.author | Lakovits, Karin | |
dc.contributor.author | Korosec, Ana | |
dc.contributor.author | Martins, Rui | |
dc.contributor.author | Kral, Julia B | |
dc.contributor.author | Mesteri, Ildiko | |
dc.contributor.author | Strobl, Birgit | |
dc.contributor.author | Müller, Mathias | |
dc.contributor.author | Kalinke, Ulrich | |
dc.contributor.author | Merad, Miriam | |
dc.contributor.author | Knapp, Sylvia | |
dc.date.accessioned | 2018-03-05T15:17:58Z | |
dc.date.available | 2018-03-05T15:17:58Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice. 2016, 46 (9):2175-86 Eur. J. Immunol. | en |
dc.identifier.issn | 1521-4141 | |
dc.identifier.pmid | 27312374 | |
dc.identifier.doi | 10.1002/eji.201546201 | |
dc.identifier.uri | http://hdl.handle.net/10033/621304 | |
dc.description.abstract | Protecting the integrity of the lung epithelial barrier is essential to ensure respiration and proper oxygenation in patients suffering from various types of lung inflammation. Type I interferon (IFN-I) has been associated with pulmonary epithelial barrier function, however, the mechanisms and involved cell types remain unknown. We aimed to investigate the importance of IFN-I with respect to its epithelial barrier strengthening function to better understand immune-modulating effects in the lung with potential medical implications. Using a mouse model of pneumococcal pneumonia, we revealed that IFN-I selectively protects alveolar epithelial type II cells (AECII) from inflammation-induced cell death. Mechanistically, signaling via the IFN-I receptor on AECII is sufficient to promote AECII survival. The net effects of IFN-I are barrier protection, together with diminished tissue damage, inflammation, and bacterial loads. Importantly, we found that the protective role of IFN-I can also apply to sterile acute lung injury, in which loss of IFN-I signaling leads to a significant reduction in barrier function caused by AECII cell death. Our data suggest that IFN-I is an important mediator in lung inflammation that plays a protective role by antagonizing inflammation-associated cell obstruction, thereby strengthening the integrity of the epithelial barrier. | |
dc.language.iso | en | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Alveolar Epithelial Cells | en |
dc.subject.mesh | Animals | en |
dc.subject.mesh | Cell Survival | en |
dc.subject.mesh | Disease Models, Animal | en |
dc.subject.mesh | Female | en |
dc.subject.mesh | Immunomodulation | en |
dc.subject.mesh | Interferon Type I | en |
dc.subject.mesh | Lung Injury | en |
dc.subject.mesh | Macrophages, Alveolar | en |
dc.subject.mesh | Mice | en |
dc.subject.mesh | Mice, Knockout | en |
dc.subject.mesh | Pneumonia, Pneumococcal | en |
dc.subject.mesh | Receptor, Interferon alpha-beta | en |
dc.subject.mesh | Signal Transduction | en |
dc.subject.mesh | Streptococcus pneumoniae | en |
dc.title | Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice. | en |
dc.type | Article | en |
dc.contributor.department | TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany. | en |
dc.identifier.journal | European journal of immunology | en |
refterms.dateFOA | 2018-06-12T16:50:01Z | |
html.description.abstract | Protecting the integrity of the lung epithelial barrier is essential to ensure respiration and proper oxygenation in patients suffering from various types of lung inflammation. Type I interferon (IFN-I) has been associated with pulmonary epithelial barrier function, however, the mechanisms and involved cell types remain unknown. We aimed to investigate the importance of IFN-I with respect to its epithelial barrier strengthening function to better understand immune-modulating effects in the lung with potential medical implications. Using a mouse model of pneumococcal pneumonia, we revealed that IFN-I selectively protects alveolar epithelial type II cells (AECII) from inflammation-induced cell death. Mechanistically, signaling via the IFN-I receptor on AECII is sufficient to promote AECII survival. The net effects of IFN-I are barrier protection, together with diminished tissue damage, inflammation, and bacterial loads. Importantly, we found that the protective role of IFN-I can also apply to sterile acute lung injury, in which loss of IFN-I signaling leads to a significant reduction in barrier function caused by AECII cell death. Our data suggest that IFN-I is an important mediator in lung inflammation that plays a protective role by antagonizing inflammation-associated cell obstruction, thereby strengthening the integrity of the epithelial barrier. |