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Journal of Virology, February 2005, p. 2050-2057, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2050-2057.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Role of CCL11 in Eosinophilic Lung Disease during Respiratory Syncytial Virus Infection

Stephen P. Matthews ,1,{dagger},{ddagger} John S. Tregoning,1,{dagger} Anthony J. Coyle,2 Tracy Hussell,1,§ and Peter J. M. Openshaw1*

Department of Respiratory Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom,1 Department of Biology, Inflammation Division, Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts2

Received 27 May 2004/ Accepted 4 October 2004

Respiratory syncytial virus (RSV) is a major viral pathogen of infants and the elderly. Significant morbidity is caused by an overexuberant mixed lung cell infiltrate, which is thought to be driven by chemokines. One of the main chemotactic mediators responsible for the movement of eosinophils is CCL11 (eotaxin). Using a mouse model of eosinophilic bronchiolitis induced by RSV, we show here that treatment in vivo with a blocking antibody to CCL11 greatly reduces lung eosinophilia and disease severity. In addition, anti-CCL11 caused a striking inhibition of CD4-T-cell influx and shifted cytokine production away from interleukin-5 without reducing the resistance to viral replication. These results suggest that in addition to influencing eosinophil diapedesis and survival, anti-CCL11 has an action on T cells. These studies strengthen the case for anti-CCL11 treatment of Th2-driven diseases.

* Corresponding author. Mailing address: Department of Respiratory Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London W2 1PG, United Kingdom. Phone: (44) 20 7594 3854. Fax: (44) 20 7262 8913. E-mail: p.openshaw{at}imperial.ac.uk.

{dagger} S.P.M. and J.S.T. contributed equally to this work.

{ddagger} Present address: Division of Cell Biology and Immunology, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom.

§ Present address: Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College London, London SW7 2AZ, United Kingdom.

Journal of Virology, February 2005, p. 2050-2057, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2050-2057.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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