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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.

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Trypanolytic activity of TNF-α on both  monomorphic and pleomorphic bloodstream forms of T.  brucei. Lysis assays were carried out at 30°C in the presence of different concentrations of TNF-α as described  in Materials and Methods.  (a) Monomorphic T. brucei  parasites, isolated at the  early stage (▪) and the peak  (□) of the parasitaemia, were  incubated with TNF-α. The  percentage of TNF-α–specific lysis was calculated as  described in Materials and  Methods. (b) Pleomorphic T.  brucei parasites, isolated at  the early stage (▪) and peak  (□) of the parasitaemia, were  incubated with TNF-α, the  same way as the monomorphic parasites.
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Figure 10: Trypanolytic activity of TNF-α on both monomorphic and pleomorphic bloodstream forms of T. brucei. Lysis assays were carried out at 30°C in the presence of different concentrations of TNF-α as described in Materials and Methods. (a) Monomorphic T. brucei parasites, isolated at the early stage (▪) and the peak (□) of the parasitaemia, were incubated with TNF-α. The percentage of TNF-α–specific lysis was calculated as described in Materials and Methods. (b) Pleomorphic T. brucei parasites, isolated at the early stage (▪) and peak (□) of the parasitaemia, were incubated with TNF-α, the same way as the monomorphic parasites.

Mentions: To analyze whether different developmental stages of T. brucei differ in sensitivity towards TNF-α, lysis experiments were performed at 30°C on both monomorphic and pleomorphic AnTat 1.1 trypanosomes isolated at the initial phase of the parasitaemia and at the peak of the parasitaemia. As shown in Fig. 10, a and b, TNF-α–mediated lysis of both monomorphic and pleomorphic trypanosomes occurred only when these bloodstream parasites were isolated at the peak of the parasitaemia, while no lytic effect was observed when parasites were isolated at the beginning of the infection. These results point again to a heterogeneity of trypanosomes with respect to their susceptibility to 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)

Trypanolytic activity of TNF-α on both  monomorphic and pleomorphic bloodstream forms of T.  brucei. Lysis assays were carried out at 30°C in the presence of different concentrations of TNF-α as described  in Materials and Methods.  (a) Monomorphic T. brucei  parasites, isolated at the  early stage (▪) and the peak  (□) of the parasitaemia, were  incubated with TNF-α. The  percentage of TNF-α–specific lysis was calculated as  described in Materials and  Methods. (b) Pleomorphic T.  brucei parasites, isolated at  the early stage (▪) and peak  (□) of the parasitaemia, were  incubated with TNF-α, the  same way as the monomorphic parasites.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 10: Trypanolytic activity of TNF-α on both monomorphic and pleomorphic bloodstream forms of T. brucei. Lysis assays were carried out at 30°C in the presence of different concentrations of TNF-α as described in Materials and Methods. (a) Monomorphic T. brucei parasites, isolated at the early stage (▪) and the peak (□) of the parasitaemia, were incubated with TNF-α. The percentage of TNF-α–specific lysis was calculated as described in Materials and Methods. (b) Pleomorphic T. brucei parasites, isolated at the early stage (▪) and peak (□) of the parasitaemia, were incubated with TNF-α, the same way as the monomorphic parasites.
Mentions: To analyze whether different developmental stages of T. brucei differ in sensitivity towards TNF-α, lysis experiments were performed at 30°C on both monomorphic and pleomorphic AnTat 1.1 trypanosomes isolated at the initial phase of the parasitaemia and at the peak of the parasitaemia. As shown in Fig. 10, a and b, TNF-α–mediated lysis of both monomorphic and pleomorphic trypanosomes occurred only when these bloodstream parasites were isolated at the peak of the parasitaemia, while no lytic effect was observed when parasites were isolated at the beginning of the infection. These results point again to a heterogeneity of trypanosomes with respect to their susceptibility to 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