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© The Rockefeller University Press, 0021-9525/1997//715 $5.00
The Journal of Cell Biology, Volume 137, Number 3, , 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.

1. Abbreviations used in this paper: FSC, forward scatter; IFN-, interferon-; TEM, transmission electron microscopy; TNF-, tumor necrosis factor-; VAT, variable antigen type; VSG, variant-specific surface glycoprotein.

M. Geuskens is a senior research associate of the Belgian National Fund for Scientific Research. This investigation received financial support from the United Nations Development Program/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases, the Belgian National Fund for Scientific Research (n G.0325.95), and the Flemish Government (Vlaams Actieprogramma Biotechnologie; VLAB). This investigation was performed under an Interuniversity Attraction Pole Programme financed by the Belgian state Diensten van de Eerste Minister–Federale diensten voor wetenschappelijke, technische en cuturele aangelegenheden.

Please address all correspondence to S. Magez, Eenheid CIMM (IMOL II), Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, Sint Genesius Rode 1640, Belgium. Tel.: 32-2-359-03-58; Fax: 32-2-359-03-59.

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