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Science 314 (5798): 454-458

Copyright © 2006 by the American Association for the Advancement of Science

Dendritic Cell Stimulation by Mycobacterial Hsp70 Is Mediated Through CCR5

R. Andres Floto,1* Paul A. MacAry,1,2* Jessica M. Boname,1 Tan Suet Mien,3 Beate Kampmann,4 James R. Hair,1 Oh Seen Huey,2 Edith N. G. Houben,5 Jean Pieters,5 Cheryl Day,6 Wulf Oehlmann,7 Mahavir Singh,7 Kenneth G. C. Smith,1 Paul J. Lehner1{dagger}

Abstract: An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.

1 Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
2 Immunology Program, Department of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
3 Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, Singapore.
4 Department of Paediatrics and Wellcome Centre for Clinical Tropical Medicine, Imperial College London, UK.
5 Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
6 Nuffield Department of Medicine, The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK.
7 Lionex Diagnostics and Therapeutics GmbH, Mascheroder Weg 1b, D-38124, Braunschweig, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: pjl30{at}cam.ac.uk


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