The Journal of Experimental Medicine
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Published 21 November 2005. doi:10.1084/jem.20050955
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 10, 1319-1325
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BRIEF DEFINITIVE REPORT

 Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity

Philip Smith1, Rosie E. Fallon1, Niamh E. Mangan1, Caitriona M. Walsh1, Margarida Saraiva2, Jon R. Sayers3, Andrew N.J. McKenzie4, Antonio Alcami2,5, and Padraic G. Fallon1

1 School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
2 Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CBQ 2QQ, England, UK
3 Henry Wellcome Laboratories for Medical Research, University of Sheffield, Sheffield S10 2TN, England UK
4 The Medical Research Council Laboratory of Molecular Biology, Cambridge CBQ 2QH, England, UK
5 Centro Nacional de Biotecnologia, Campus de Cantoblanco, 28049 Madrid, Spain

CORRESPONDENCE Padraic G. Fallon: pfallon{at}tcd.ie

The coevolution of humans and infectious agents has exerted selective pressure on the immune system to control potentially lethal infections. Correspondingly, pathogens have evolved with various strategies to modulate and circumvent the host's innate and adaptive immune response. Schistosoma species are helminth parasites with genes that have been selected to modulate the host to tolerate chronic worm infections, often for decades, without overt morbidity. The modulation of immunity by schistosomes has been shown to prevent a range of immune-mediated diseases, including allergies and autoimmunity. Individual immune-modulating schistosome molecules have, therefore, therapeutic potential as selective manipulators of the immune system to prevent unrelated diseases. Here we show that S. mansoni eggs secrete a protein into host tissues that binds certain chemokines and inhibits their interaction with host chemokine receptors and their biological activity. The purified recombinant S. mansoni chemokine binding protein (smCKBP) suppressed inflammation in several disease models. smCKBP is unrelated to host proteins and is the first described chemokine binding protein encoded by a pathogenic human parasite and may have potential as an antiinflammatory agent.

M. Saraiva's present address is National Institute for Medical Research, London NW7 1AA, England, UK.


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