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Journal of Virology, May 2008, p. 4441-4448, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.02541-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Alveolar Macrophages Are a Major Determinant of Early Responses to Viral Lung Infection but Do Not Influence Subsequent Disease Development{triangledown}

Philippa K. Pribul,1,{dagger} James Harker,1,{dagger} Belinda Wang,1 Hongwei Wang,2 John S. Tregoning,1 Jürgen Schwarze,2 and Peter J. M. Openshaw1*

Department of Respiratory Medicine, the Centre for Respiratory Research and the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, National Heart and Lung Institute, Imperial College London, St. Mary's Campus, London W2 1PG, United Kingdom,1 Centre for Inflammation Research, University of Edinburgh, the Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom2

Received 28 November 2007/ Accepted 6 February 2008

Macrophages are abundant in the lower respiratory tract. They play a central role in the innate response to infection but may also modulate excessive inflammation. Both macrophages and ciliated epithelial cells respond to infection by releasing soluble mediators, leading to the recruitment of innate and adaptive effector cells. To study the role of lung macrophages in acute respiratory viral infection, we depleted them by the inhalation of clodronate liposomes in an established mouse model of respiratory syncytial virus (RSV) disease. Infection caused an immediate local release of inflammatory cytokines and chemokines, peaking on day 1, which was virtually abolished by clodronate liposome treatment. Macrophage depletion inhibited the activation (days 1 to 2) and recruitment (day 4) of natural killer (NK) cells and enhanced peak viral load in the lung (day 4). However, macrophage depletion did not affect the recruitment of activated CD4 or CD8 T cells, weight loss, or virus-induced changes in lung function. Therefore, lung macrophages play a central role in the early responses to viral infection but have remarkably little effect on the adaptive response occurring at the time of peak disease severity.

* Corresponding author. Mailing address: Department of Respiratory Medicine, Paddington Campus of Imperial College, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 20 7594 3854. Fax: 44 20 7262 8913. E-mail: p.openshaw{at}imperial.ac.uk

{triangledown} Published ahead of print on 20 February 2008.

{dagger} These authors contributed equally to this paper.

Journal of Virology, May 2008, p. 4441-4448, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.02541-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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