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Specific Uptake of Tumor Necrosis Factor-α 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
The Journal of Cell Biology
Vol. 137, No. 3 (May 5, 1997), pp. 715-727
Stable URL: http://www.jstor.org/stable/1618045
Page Count: 13
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Specific Uptake of Tumor Necrosis Factor-α Is Involved in Growth Control of Trypanosoma brucei
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Abstract

Trypanosoma brucei is lysed by tumor necrosis factor-α (TNF-α) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF-α-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-α 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-α 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-α is involved in the growth control of T. brucei.

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