title: Limitation of Trypanosoma brucei parasitaemia results from density-dependent parasite differentiation and parasite killing by the host immune response.
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.
authors.affiliation: Department of Pathology, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611, USA. k-tyler@northwestern.edu
authors.forename: K M
authors.initials: KM
authors.lastname: Tyler
authors.forename: P G
authors.initials: PG
authors.lastname: Higgs
authors.forename: K R
authors.initials: KR
authors.lastname: Matthews
authors.forename: K
authors.initials: K
authors.lastname: Gull
mesh_terms: D000818:Animals; D003198:Computer Simulation; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006790:Host-Parasite Interactions; D008432:Mathematical Computing; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018512:Parasitemia / Q000276:immunology* / Q000469:parasitology; D011156:Population Density; D014346:Trypanosoma brucei brucei / Q000254:growth & development* / Q000276:immunology; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000469:parasitology
chemical_list: D008058:Dihydrolipoamide Dehydrogenase