Limitation of Trypanosoma brucei parasitaemia results from density-dependent parasite differentiation and parasite killing by the host immune response. |
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Authors: | K M Tyler P G Higgs K R Matthews K Gull |
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Affiliation: | Department of Pathology, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611, USA. k-tyler@northwestern.edu |
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Abstract: | 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. |
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