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*Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia;
World Health Organisation Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia; and
Departments of Pharmacology and Medicine, University of Melbourne, Melbourne, Victoria, Australia
The clinical response to influenza infection ranges from mild disease to severe pneumonia and it remains unclear whether the inflammatory response to infection is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease. Infection of neutrophil-depleted mice with influenza virus HKx31 (H3N2) led to rapid weight loss, pneumonia, and death. Neutropenia was associated with enhanced virus replication in the respiratory tract; however, viral titers were declining at the time of death, leading us to investigate other factors contributing to mortality. In addition to thymic atrophy, lymphopenia, and viremic spread, depletion of neutrophils led to exacerbated pulmonary inflammation, edema, and respiratory dysfunction. Thus, while it is well established that neutrophils contribute to lung injury in a range of pathological conditions, reduced numbers or impaired neutrophil function can facilitate progression of mild influenza to severe clinical disease.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by Project Grant 400226 from the National Health and Medical Research Council of Australia. P.C.R. is a National Health and Medical Research Council R. D. Wright Research Fellow. The Melbourne World Health Organisation Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health and Ageing.
2 Address correspondence and reprint requests to Dr. Patrick C. Reading, Department of Microbiology and Immunology, University of Melbourne, Melbourne, 3010, Victoria, Australia. E-mail address: preading{at}unimelb.edu.au
3 Abbreviations used in this paper: DC, dendritic cell; ARDS, acute respiratory distress syndrome; BAL, bronchoalveolar lavage; cDC, conventional DC; DN, double negative; DP, double positive; i.n., intranasal(ly); MDCK, Madin-Darby canine kidney; pDC, plasmacytoid DC; PI, propidium iodide; SP, single positive.
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