Format

Send to

Choose Destination
Eur J Immunol. 2016 Sep;46(9):2175-86. doi: 10.1002/eji.201546201. Epub 2016 Jul 12.

Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice.

Author information

1
CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
2
Laboratory of Infection Biology, Department of Medicine I, Medical University, Vienna, Austria.
3
Center for Physiology and Pharmacology, Institute for Physiology, Medical University of Vienna, Vienna, Austria.
4
Pathology Überlingen, Überlingen, Germany.
5
Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria.
6
Institute for Experimental Infection Research, TWINCORE, Center for Experimental and Clinical Infection Research, Helmholtz Center for Infection Research, Braunschweig, Germany.
7
Hannover Medical School, Hannover, Germany.
8
Department of Oncological Science, The Tisch Cancer Institute and the Immunology Institute, Mount Sinai School of Medicine, New York, New York.
9
CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. sylvia.knapp@meduniwien.ac.at.
10
Laboratory of Infection Biology, Department of Medicine I, Medical University, Vienna, Austria. sylvia.knapp@meduniwien.ac.at.

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.

KEYWORDS:

Acute lung injury; Alveolar epithelial cells; Epithelial barrier; Pneumococcal pneumonia; Type I interferon

PMID:
27312374
PMCID:
PMC5370074
DOI:
10.1002/eji.201546201
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center