Limitation of Trypanosoma brucei parasitaemia results from density-dependent parasite differentiation and parasite killing by the host immune response

In the bloodstream of its mammalian host, the 'slender' form of Trypanosoma brucei replicates extracellularly, producing a parasitaemia. At high density, the level of parasitaemia is limited at a sublethal level by differentiation to the non-replicative 'stumpy' form and by the h...

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Veröffentlicht in:Proceedings of the Royal Society. B, Biological sciences Biological sciences, 2001-11, Vol.268 (1482), p.2235-2243
Hauptverfasser: Tyler, Kevin M., Higgs, Paul G., Matthews, Keith R., Gull, Keith
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Sprache:eng
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Zusammenfassung:In the bloodstream of its mammalian host, the 'slender' form of Trypanosoma brucei replicates extracellularly, producing a parasitaemia. At high density, the level of parasitaemia is limited at a sublethal level by differentiation to the non-replicative 'stumpy' form and by the host immune response. Here, we derive continuous time equations to model the time-course, cell types and level of trypanosome parasitaemia, and compare the best fits with experimental data. The best fits that were obtained favour a model in which both density-dependent trypanosome differentiation and host immune response have a role in limiting the increase of parasites, much poorer fits being obtained when differentiation and immune response are considered independently of one another. Best fits also favour a model in which the slender-to-stumpy differentiation progresses in a manner that is essentially independent of the cell cycle. Finally, these models also make the prediction that the density-dependent trypanosome differentiation mechanism can give rise to oscillations in parasitaemia level. These oscillations are independent of the immune system and are not due to antigenic variation.
ISSN:0962-8452
1471-2954
DOI:10.1098/rspb.2001.1794