Journal article

Publication year: 2013

Journal: PLoS Pathogens

Volume number: 9

Issue number: 2

ISSN: 1553-7366

eISSN: 1553-7374

Open access status: Gold

DOI Link: https://doi.org/10.1371/journal.ppat.1003188

Publisher: Public Library of Science

Abstract: 
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-beta significantly contributes to IV-induced alveolar epithelial cell (AEC) injury by autocrine induction of the proapoptotic 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-beta release in AM in a protein kinase R- (PKR-) and NF-kappa B-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-beta 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-beta-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.

Harvard Citation style: Hoegner, K., Wolff, T., Pleschka, S., Plog, S., Gruber, A., Kalinke, U., et al. (2013) Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia, PLoS Pathogens, 9(2), Article e1003188. https://doi.org/10.1371/journal.ppat.1003188

APA Citation style: Hoegner, K., Wolff, T., Pleschka, S., Plog, S., Gruber, A., Kalinke, U., Walmrath, H., Bodner, J., Gattenloehner, S., Lewe-Schlosser, P., Matrosovich, M., Seeger, W., Lohmeyer, J., & Herold, S. (2013). Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia. PLoS Pathogens. 9(2), Article e1003188. https://doi.org/10.1371/journal.ppat.1003188