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, Patrick De Baetselier

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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.

Original languageEnglish (US)
Pages (from-to)715-727
Number of pages13
JournalJournal of Cell Biology
Volume137
Issue number3
DOIs
StatePublished - May 5 1997

ASJC Scopus subject areas

  • Cell Biology

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    Magez, S., Geuskens, M., Beschin, A., Del Favero, H., Verschueren, H., Lucas, R., Pays, E., & De Baetselier, P. (1997). Specific uptake of tumor necrosis factor-α is involved in growth control of Trypanosoma brucei. Journal of Cell Biology, 137(3), 715-727. https://doi.org/10.1083/jcb.137.3.715