Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection

• Published in: PloS one Vol. 7; no. 3; p. e32947
• Main Authors: Hsu, Alan C-Y, Parsons, Kristy, Barr, Ian, Lowther, Sue, Middleton, Deborah, Hansbro, Philip M, Wark, Peter A B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.03.2012; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Apoptosis; Avian influenza; Avian influenza viruses; Biological response modifiers; Biology; Bronchi - cytology; Bronchi - virology; Cell Line; Constraining; Cycloheximide - pharmacology; Disease susceptibility; Dogs; Endocytosis; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - virology; Glycoproteins; Health aspects; Human behavior; Humans; Immune response; Immune system; Infection; Infections; Influenza; Influenza A Virus, H3N2 Subtype - metabolism; Influenza A Virus, H5N1 Subtype - metabolism; Influenza, Human - metabolism; Innate immunity; Interferon; Interferon Type I - metabolism; Interferon-beta - metabolism; Kinases; Medicine; Models, Biological; N-Acetylneuraminic Acid - chemistry; Organic acids; Pandemics; Protein Synthesis Inhibitors - pharmacology; Receptors; Replication; Respiratory tract; Signaling; Virus diseases; Virus replication; Viruses; Australia; New South Wales Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032947

Innate antiviral responses in bronchial epithelial cells (BECs) provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs). However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.