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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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TNF-α–mediated lysis of bloodstream forms of T. brucei as function of temperature and time. A lysis assay was performed using a TNF-α concentration of 104 U/ml. Samples were  kept at the indicated temperatures for various periods of time, up  till the moment that a plateau of TNF-α–specific lysis was reached.  The percentage of lysis was calculated as described in Materials  and Methods.
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Figure 6: TNF-α–mediated lysis of bloodstream forms of T. brucei as function of temperature and time. A lysis assay was performed using a TNF-α concentration of 104 U/ml. Samples were kept at the indicated temperatures for various periods of time, up till the moment that a plateau of TNF-α–specific lysis was reached. The percentage of lysis was calculated as described in Materials and Methods.

Mentions: Incubations of parasites at 4°C with TNF-α–gold particles yielded a very rare labeling of the lumen of the flagellar pocket, and at this temperature no lysis was recorded, not even after 24 h of incubation (results not shown). To evaluate to which extent TNF-α–mediated trypanolysis is temperature dependent, experiments with monomorphic AnTat 1.1 trypanosomes were performed in parallel at different temperatures ranging from 37° to 17°C. According to the results shown in Fig. 6, the same maximal lysis was obtained at 37°, 32°, or 29°C, although the incubation time required to reach the lytic plateau value increased slightly with lower temperatures. At 26°C, ∼50% of the maximal TNF-α–mediated lysis was recorded, and practically no lysis was observed at lower temperatures, not even when samples were incubated up to 18 h.


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)

TNF-α–mediated lysis of bloodstream forms of T. brucei as function of temperature and time. A lysis assay was performed using a TNF-α concentration of 104 U/ml. Samples were  kept at the indicated temperatures for various periods of time, up  till the moment that a plateau of TNF-α–specific lysis was reached.  The percentage of lysis was calculated as described in Materials  and Methods.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: TNF-α–mediated lysis of bloodstream forms of T. brucei as function of temperature and time. A lysis assay was performed using a TNF-α concentration of 104 U/ml. Samples were kept at the indicated temperatures for various periods of time, up till the moment that a plateau of TNF-α–specific lysis was reached. The percentage of lysis was calculated as described in Materials and Methods.
Mentions: Incubations of parasites at 4°C with TNF-α–gold particles yielded a very rare labeling of the lumen of the flagellar pocket, and at this temperature no lysis was recorded, not even after 24 h of incubation (results not shown). To evaluate to which extent TNF-α–mediated trypanolysis is temperature dependent, experiments with monomorphic AnTat 1.1 trypanosomes were performed in parallel at different temperatures ranging from 37° to 17°C. According to the results shown in Fig. 6, the same maximal lysis was obtained at 37°, 32°, or 29°C, although the incubation time required to reach the lytic plateau value increased slightly with lower temperatures. At 26°C, ∼50% of the maximal TNF-α–mediated lysis was recorded, and practically no lysis was observed at lower temperatures, not even when samples were incubated up to 18 h.

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