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

Magez S, Geuskens M, Beschin A, del Favero H, Verschueren H, Lucas R, Pays E, de Baetselier P - J. Cell Biol. (1997)

Bottom Line: The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Belgium.

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.

Show MeSH

Related in: MedlinePlus

Lysis of bloodstream forms of T. brucei in function of  time (hours) and concentration of TNF-α: 1 U/ml (□), 10 U/ml  (▪), 102 U/ml (○), 103 U/ml (•), 104 U/ml (⋄), 105 U/ml (♦), and  106 U/ml (+). Trypanosomes were isolated from the blood of an  infected mouse and incubated for up to 8 h in PSG (pH 8.0) at  30°C. Lysis assays were performed, and the percentage of lysis  was calculated as described in Materials and Methods. Each concentration of TNF-α was tested in at least three independent experiments, and a representative experiment is shown.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2139880&req=5

Figure 1: Lysis of bloodstream forms of T. brucei in function of time (hours) and concentration of TNF-α: 1 U/ml (□), 10 U/ml (▪), 102 U/ml (○), 103 U/ml (•), 104 U/ml (⋄), 105 U/ml (♦), and 106 U/ml (+). Trypanosomes were isolated from the blood of an infected mouse and incubated for up to 8 h in PSG (pH 8.0) at 30°C. Lysis assays were performed, and the percentage of lysis was calculated as described in Materials and Methods. Each concentration of TNF-α was tested in at least three independent experiments, and a representative experiment is shown.

Mentions: Monomorphic AnTat 1.1 trypanosomes, isolated from the blood of infected mice, were incubated up to 8 h at 30°C in PSG containing different concentrations of recombinant murine TNF-α to follow trypanolysis as a function of time. As shown in Fig. 1, a dose-dependent lysis of the parasites was recorded, starting between 3 to 4 h of incubation and reaching maximal levels after 5 h of incubation. No significant lysis was recorded in the absence of TNF-α.


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

Magez S, Geuskens M, Beschin A, del Favero H, Verschueren H, Lucas R, Pays E, de Baetselier P - J. Cell Biol. (1997)

Lysis of bloodstream forms of T. brucei in function of  time (hours) and concentration of TNF-α: 1 U/ml (□), 10 U/ml  (▪), 102 U/ml (○), 103 U/ml (•), 104 U/ml (⋄), 105 U/ml (♦), and  106 U/ml (+). Trypanosomes were isolated from the blood of an  infected mouse and incubated for up to 8 h in PSG (pH 8.0) at  30°C. Lysis assays were performed, and the percentage of lysis  was calculated as described in Materials and Methods. Each concentration of TNF-α was tested in at least three independent experiments, and a representative experiment is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139880&req=5

Figure 1: Lysis of bloodstream forms of T. brucei in function of time (hours) and concentration of TNF-α: 1 U/ml (□), 10 U/ml (▪), 102 U/ml (○), 103 U/ml (•), 104 U/ml (⋄), 105 U/ml (♦), and 106 U/ml (+). Trypanosomes were isolated from the blood of an infected mouse and incubated for up to 8 h in PSG (pH 8.0) at 30°C. Lysis assays were performed, and the percentage of lysis was calculated as described in Materials and Methods. Each concentration of TNF-α was tested in at least three independent experiments, and a representative experiment is shown.
Mentions: Monomorphic AnTat 1.1 trypanosomes, isolated from the blood of infected mice, were incubated up to 8 h at 30°C in PSG containing different concentrations of recombinant murine TNF-α to follow trypanolysis as a function of time. As shown in Fig. 1, a dose-dependent lysis of the parasites was recorded, starting between 3 to 4 h of incubation and reaching maximal levels after 5 h of incubation. No significant lysis was recorded in the absence of TNF-α.

Bottom Line: The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Belgium.

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.

Show MeSH
Related in: MedlinePlus