J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/05/715/13 $2.00
Volume 137, Number 3, May 5, 1997 715-727

Specific Uptake of Tumor Necrosis Factor- Is Involved in Growth Control of Trypanosoma brucei

Stefan Magez,^* Maurice Geuskens, Alain Beschin,^* Herwig del Favero,^* Hendrik Verschueren,^§ Ralf Lucas,^* Etienne Pays, and Patrick de Baetselier^*

^* Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel and  Department of Molecular Parasitology, Université Libre de Bruxelles, Belgium; and ^§ Cell Biology Unit, Pasteur Institute, 1180 Brussels, Belgium

Trypanosoma brucei is lysed by tumor necrosis factor- (TNF-) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF--gold particles are endocytosed via coated pits and vesicles and are directed towards lysosome-like digestive organelles. The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity. TNF- specific lysis is prevented when lysis assays are performed at a temperature <26°C, despite uptake of the cytokine. Inhibition of lysis is also observed when a lysosomotropic agent is added during the first 2 h of incubation. Both monomorphic and pleomorphic trypanosomes are lysed but only when isolated during the peak of parasitaemia. Lysis is not observed with early infection stage parasites or procyclic (insect-specific) forms. Anti- TNF- treatment of T. brucei-infected mice reveals a dramatic increase in parasitaemia in the blood circulation, the spleen, the lymph nodes, and the peritoneal cavity. These data suggest that in the mammalian host, TNF- is involved in the growth control of T. brucei.

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