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A glycosylphosphatidylinositol-based treatment alleviates trypanosomiasis-associated immunopathology

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dc.contributor.author Stijlemans, B. en_US
dc.contributor.author Baral, T. N. en_US
dc.contributor.author Guilliams, M. en_US
dc.contributor.author Brys, L. en_US
dc.contributor.author Korf, J. en_US
dc.contributor.author Drennan, M. en_US
dc.contributor.author Van Den Abbeele, J. en_US
dc.contributor.author De Baetselier, P. en_US
dc.contributor.author Magez, S. en_US
dc.date.accessioned 2007-12-06T14:34:11Z
dc.date.available 2007-12-06T14:34:11Z
dc.date.issued 2007 en_US
dc.identifier.issn 0022-1767 en_US
dc.identifier.other ITG-P7A en_US
dc.identifier.other PARAS en_US
dc.identifier.other U-ENTOM en_US
dc.identifier.other JIF en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.uri http://hdl.handle.net/10390/283
dc.description.abstract The GPI-anchored trypanosome variant surface glycoprotein (VSG) triggers macrophages to produce TNF, involved in trypanosomiasis-associated inflammation and the clinical manifestation of sleeping sickness. Aiming at inhibiting immunopathology during experimental Trypanosoma brucei infections, a VSG-derived GPI-based treatment approach was developed. To achieve this, mice were exposed to the GPI before an infectious trypanosome challenge. This GPI-based strategy resulted in a significant prolonged survival and a substantial protection against infection-associated weight loss, liver damage, acidosis, and anemia; the latter was shown to be Ab-independent and correlated with reduced macrophage-mediated RBC clearance. In addition, GPI-based treatment resulted in reduced circulating serum levels of the inflammatory cytokines TNF and IL-6, abrogation of infection-induced LPS hypersensitivity, and an increase in circulating IL-10. At the level of trypanosomiasis-associated macrophage activation, the GPI-based treatment resulted in an impaired secretion of TNF by VSG and LPS pulsed macrophages, a reduced expression of the inflammatory cytokine genes TNF, IL-6, and IL-12, and an increased expression of the anti-inflammatory cytokine gene IL-10. In addition, this change in cytokine pattern upon GPI-based treatment was associated with the expression of alternatively activated macrophage markers. Finally, the GPI-based treatment also reduced the infection-associated pathology in Trypanosoma congolense and Trypanosoma evansi model systems as well as in tsetse fly challenge experiments, indicating potential field applicability for this intervention strategy. en_US
dc.language English en_US
dc.subject Protozoal diseases en_US
dc.subject Trypanosomiasis, African en_US
dc.subject Trypanosoma brucei en_US
dc.subject Trypanosoma congolense en_US
dc.subject Trypanosoma evansi en_US
dc.subject Immunopathology en_US
dc.subject Drug development en_US
dc.subject Glycosylphosphatidylinositol en_US
dc.subject Macrophages en_US
dc.title A glycosylphosphatidylinositol-based treatment alleviates trypanosomiasis-associated immunopathology en_US
dc.type Article en_US
dc.citation.issue 6 en_US
dc.citation.jtitle Journal of Immunology en_US
dc.citation.volume 179 en_US
dc.citation.pages 4003-4014 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/17785839
dc.citation.jabbreviation J Immunol en_US


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