Specific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei.

TitleSpecific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei.
Publication TypeJournal Article
Year of Publication1997
AuthorsMagez, S., M. Geuskens, A. Beschin, H. del Favero, H. Verschueren, R. Lucas, E. Pays, and P. De Baetselier
JournalJ Cell Biol
Volume137
Issue3
Pagination715-27
Date Published1997 May 5
ISSN0021-9525
KeywordsAmino Acid Sequence, Animals, Antibodies, Monoclonal, Binding Sites, Hydrogen-Ion Concentration, Lysosomes, Mice, Microscopy, Electron, Molecular Sequence Data, Peptides, Protozoan Proteins, Temperature, Trypanosoma brucei brucei, Tumor Necrosis Factor-alpha, Water-Electrolyte Balance
Abstract

Trypanosoma brucei is lysed by tumor necrosis factor-alpha (TNF-alpha) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF-alpha-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-alpha specific lysis is prevented when lysis assays are performed at a temperature <26 degrees 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-alpha 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-alpha is involved in the growth control of T. brucei.

Alternate JournalJ. Cell Biol.
PubMed ID9151676
PubMed Central IDPMC2139880