{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:57:49Z","timestamp":1791262669745,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>","DOI":"10.4049\/jimmunol.179.6.4003","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:32:36Z","timestamp":1397849556000},"page":"4003-4014","source":"Crossref","is-referenced-by-count":70,"title":["A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology"],"prefix":"10.1093","volume":"179","author":[{"given":"Benoi\u0302t","family":"Stijlemans","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels , Pleinlaan 2, Brussels, Belgium VIB, Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toya Nath","family":"Baral","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels , Pleinlaan 2, Brussels, Belgium VIB, Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Guilliams","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels , Pleinlaan 2, Brussels, Belgium VIB, Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Brys","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels , Pleinlaan 2, Brussels, Belgium VIB, Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Korf","sequence":"additional","affiliation":[{"name":"Institute Pasteur, Department of Mycobacterial Immunology , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Drennan","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels , Pleinlaan 2, Brussels, Belgium VIB, Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Van Den Abbeele","sequence":"additional","affiliation":[{"name":"Unit of Entomology, Prins Leopold Institute of Tropical Medicine (ITM) , Antwerp ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"De Baetselier","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels , Pleinlaan 2, Brussels, Belgium VIB, Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Magez","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels , Pleinlaan 2, Brussels, Belgium VIB, Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,9,15]]},"reference":[{"key":"2026012809303710000_R1","first-page":"247","volume-title":"Vet. 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