critical role of constitutive type i interferon response in bronchial epithelial cell to influenza infection关键作用的本构i型干扰素反应流感感染的支气管上皮细胞.pdf

Critical Role of Constitutive Type I Interferon Response in Bronchial Epithelial Cell to Influenza Infection 1 1 2 3 3 1 Alan C-Y. Hsu *, Kristy Parsons , Ian Barr , Sue Lowther , Deborah Middleton , Philip M. Hansbro , Peter A. B. Wark1,4 1 Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia, 2 World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia, 3 The Commonwealth Scientific and Industrial Research Organization (CSIRO) - Australian Animal Health Laboratory, Geelong, Victoria, Australia, 4 Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, New South Wales, Australia Abstract 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-b. However it was found that there was constitutive release of IFN-b by BECs and this was