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Research Article
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Published Online: 30 March 2011

Responses of Mouse Airway Epithelial Cells and Alveolar Macrophages to Virulent and Avirulent Strains of Influenza A Virus

Publication: Viral Immunology
Volume 24, Issue Number 2

Abstract

Influenza A virus (IAV) infection is associated with outcomes ranging from subclinical infection to severe pneumonia. In this study, we compared IAV strains BJx109 (H3N2), HKx31 (H3N2), and PR8 (H1N1), for their ability to elicit innate immune responses from mouse airway cells in vitro and their virulence in mice. The viruses differed markedly in their ability to induce disease in mice (PR8 > HKx31 > BJx109). In particular, PR8 infection was associated with high levels of virus replication and pulmonary inflammation. We next compared the ability of each virus strain to infect and induce inflammatory mediators from mouse airway cells. First, major differences were observed in the ability of viruses to infect and induce chemokines and cytokines from mouse alveolar macrophages (BJx109 > HKx31 > PR8), but not from airway epithelial cells (AEC) in vitro. Second, C-type lectins of the innate immune system in mouse lung fluids blocked the ability of BJx109, but not PR8, to infect mouse macrophages and AEC. The failure of the virulent PR8 virus to elicit responses from airway macrophages, combined with resistance to antiviral proteins in mouse airway fluids, likely contribute to virulence in mice. These findings provide insight into the mechanisms underlying disease severity in the mouse model of influenza infection.

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cover image Viral Immunology
Viral Immunology
Volume 24Issue Number 2April 2011
Pages: 77 - 88
PubMed: 21449718

History

Published in print: April 2011
Published online: 30 March 2011
Accepted: 18 December 2010
Received: 9 November 2010

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    Authors

    Affiliations

    Michelle D. Tate
    Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
    Heidi C. Schilter
    Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
    Andrew G. Brooks
    Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
    Patrick C. Reading
    Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
    WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia.

    Notes

    Address correspondence to:Dr. Patrick C. ReadingDepartment of Microbiology and ImmunologyUniversity of MelbourneRoyal ParadeVictoria, 3010,Australia
    E-mail: [email protected]

    Author Disclosure Statement

    M.D.T. carried out the majority of experiments described in this study, analyzed and interpreted data, and prepared figures for the manuscript. H.C.S. prepared the primary mouse airway epithelial cell cultures used in this study. P.C.R. and M.D.T. designed the study, and P.C.R. wrote the manuscript. A.G.B. contributed to interpretation of the data and the writing of the manuscript. All authors read and approved the final manuscript. The authors declare that no conflicting financial interests exist.

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