{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:57:01Z","timestamp":1791262621600,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2003,8,1]],"date-time":"2003-08-01T00:00:00Z","timestamp":1059696000000},"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":[[2003,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Macrophages are centrally involved in the host immune response to infection with Trypanosoma brucei rhodesiense, a protozoan parasite responsible for human sleeping sickness in Africa. During trypanosome infections, the host is exposed to parasite-derived molecules that mediate macrophage activation, specifically GPI anchor substituents associated with the shed variant surface glycoprotein (VSG), plus the host-activating agent IFN-\u03b3, which is derived from activated T cells and is essential for resistance to trypanosomes. In this study, we demonstrate that the level and timing of exposure of macrophages to IFN-\u03b3 vs GPI ultimately determine the macrophage response at the level of induced gene expression. Treatment of macrophages with IFN-\u03b3 followed by GIP-sVSG (the soluble form of VSG containing the glycosylinositolphosphate substituent that is released by parasites) stimulated the induction of gene expression, including transcription of TNF-\u03b1, IL-6, GM-CSF, and IL-12p40. In contrast, treatment of macrophages with GIP-sVSG before IFN-\u03b3 stimulation resulted in a marked reduction of IFN-\u03b3-induced responses, including transcription of inducible NO synthase and secretion of NO. Additional experiments revealed that the inhibitory activity of GIP-sVSG was associated with reduction in the level of STAT1 phosphorylation, an event required for IFN-\u03b3-induced macrophage activation. These results suggest that modulation of specific aspects of the IFN-\u03b3 response may be one mechanism by which trypanosomes overcome host resistance during African trypanosomiasis.<\/jats:p>","DOI":"10.4049\/jimmunol.171.3.1466","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:29:45Z","timestamp":1398029385000},"page":"1466-1472","source":"Crossref","is-referenced-by-count":42,"title":["Glycosylinositolphosphate Soluble Variant Surface Glycoprotein Inhibits IFN-\u03b3-Induced Nitric Oxide Production Via Reduction in STAT1 Phosphorylation in African Trypanosomiasis"],"prefix":"10.1093","volume":"171","author":[{"given":"Susan P","family":"Coller","sequence":"first","affiliation":[{"name":"University of Wisconsin Medical School , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Mansfield","sequence":"additional","affiliation":[{"name":"University of Wisconsin Medical School , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M","family":"Paulnock","sequence":"additional","affiliation":[{"name":"University of Wisconsin Medical School , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,8,1]]},"reference":[{"key":"2026020210174710100_R1","first-page":"4338","volume-title":"J. 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