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.
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21 November 2005
Brief Definitive Report|
November 21 2005
Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity
Philip Smith,
Philip Smith
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
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Rosie E. Fallon,
Rosie E. Fallon
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
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Niamh E. Mangan,
Niamh E. Mangan
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
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Caitriona M. Walsh,
Caitriona M. Walsh
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
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Margarida Saraiva,
Margarida Saraiva
2Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CBQ 2QQ, England, UK
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Jon R. Sayers,
Jon R. Sayers
3Henry Wellcome Laboratories for Medical Research, University of Sheffield, Sheffield S10 2TN, England UK
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Andrew N.J. McKenzie,
Andrew N.J. McKenzie
4The Medical Research Council Laboratory of Molecular Biology, Cambridge CBQ 2QH, England, UK
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Antonio Alcami,
Antonio Alcami
2Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CBQ 2QQ, England, UK
5Centro Nacional de Biotecnologia, Campus de Cantoblanco, 28049 Madrid, Spain
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Padraic G. Fallon
Padraic G. Fallon
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
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Philip Smith
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
Rosie E. Fallon
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
Niamh E. Mangan
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
Caitriona M. Walsh
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
Margarida Saraiva
2Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CBQ 2QQ, England, UK
Jon R. Sayers
3Henry Wellcome Laboratories for Medical Research, University of Sheffield, Sheffield S10 2TN, England UK
Andrew N.J. McKenzie
4The Medical Research Council Laboratory of Molecular Biology, Cambridge CBQ 2QH, England, UK
Antonio Alcami
2Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CBQ 2QQ, England, UK
5Centro Nacional de Biotecnologia, Campus de Cantoblanco, 28049 Madrid, Spain
Padraic G. Fallon
1School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
CORRESPONDENCE Padraic G. Fallon: [email protected]
M. Saraiva's present address is National Institute for Medical Research, London NW7 1AA, England, UK.
Received:
May 11 2005
Accepted:
September 23 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (10): 1319–1325.
Article history
Received:
May 11 2005
Accepted:
September 23 2005
Citation
Philip Smith, Rosie E. Fallon, Niamh E. Mangan, Caitriona M. Walsh, Margarida Saraiva, Jon R. Sayers, Andrew N.J. McKenzie, Antonio Alcami, Padraic G. Fallon; Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity . J Exp Med 21 November 2005; 202 (10): 1319–1325. doi: https://doi.org/10.1084/jem.20050955
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