Specific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei.
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.
Magez
S
S
Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Belgium.
Geuskens
M
M
Beschin
A
A
del Favero
H
H
Verschueren
H
H
Lucas
R
R
Pays
E
E
de Baetselier
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D015800:Protozoan Proteins / Q000378:metabolism; D013696:Temperature; D014346:Trypanosoma brucei brucei / Q000254:growth & development*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014882:Water-Electrolyte Balance
D000911:Antibodies, Monoclonal; D010455:Peptides; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha