Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice.
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.
CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Laboratory of Infection Biology, Department of Medicine I, Medical University, Vienna, Austria.
Barbara B
BB
Maier
Laboratory of Infection Biology, Department of Medicine I, Medical University, Vienna, Austria.
Anastasiya
A
Hladik
Laboratory of Infection Biology, Department of Medicine I, Medical University, Vienna, Austria.
Karin
K
Lakovits
CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Laboratory of Infection Biology, Department of Medicine I, Medical University, Vienna, Austria.
Ana
A
Korosec
CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Laboratory of Infection Biology, Department of Medicine I, Medical University, Vienna, Austria.
Rui
R
Martins
Center for Physiology and Pharmacology, Institute for Physiology, Medical University of Vienna, Vienna, Austria.
Julia B
JB
Kral
Pathology Überlingen, Überlingen, Germany.
Ildiko
I
Mesteri
Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria.
Birgit
B
Strobl
Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria.
Mathias
M
Müller
Institute for Experimental Infection Research, TWINCORE, Center for Experimental and Clinical Infection Research, Helmholtz Center for Infection Research, Braunschweig, Germany.|Hannover Medical School, Hannover, Germany.
Ulrich
U
Kalinke
Department of Oncological Science, The Tisch Cancer Institute and the Immunology Institute, Mount Sinai School of Medicine, New York, New York.
Miriam
M
Merad
CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. sylvia.knapp@meduniwien.ac.at.|Laboratory of Infection Biology, Department of Medicine I, Medical University, Vienna, Austria. sylvia.knapp@meduniwien.ac.at.
Sylvia
S
Knapp
D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D056747:Immunomodulation; D007370:Interferon Type I / Q000378:metabolism*; D055370:Lung Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011018:Pneumonia, Pneumococcal / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D015398:Signal Transduction; D013296:Streptococcus pneumoniae
C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta
Acute lung injury; Alveolar epithelial cells; Epithelial barrier; Pneumococcal pneumonia; Type I interferon