title: Coincident parasite and CD8 T cell sequestration is required for development of experimental cerebral malaria.
abstract: Cerebral malaria (CM) is a fatal complication of Plasmodium falciparum infection. Using a well defined murine model, we observed the effect on disease outcome of temporarily reducing parasite burden by anti-malarial drug treatment. The anti-malarial treatment regime chosen decreased parasitaemia but did not cure the mice, allowing recrudescence of parasites. These mice were protected against CM, despite their parasitaemia having increased, following treatment cessation, to levels surpassing that associated with CM in mice not treated with the drug. The protection was associated with reduced levels of cytokines, chemokines, CD8(+) T cells and parasites in the brain. The results suggest that the development of the immunopathological response that causes CM depends on a continuous stimulus provided by parasitised red blood cells, either circulating or sequestered in small vessels.
authors.affiliation: Molecular Immunopathology Unit, The University of Sydney, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: McQuillan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mitchell
authors.forename: Yuen Fern
authors.initials: YF
authors.lastname: Ho
authors.forename: Valéry
authors.initials: V
authors.lastname: Combes
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Ball
authors.forename: Jacob
authors.initials: J
authors.lastname: Golenser
authors.forename: Georges E
authors.initials: GE
authors.lastname: Grau
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Hunt
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D008288:Malaria / Q000276:immunology* / Q000469:parasitology*; D016779:Malaria, Cerebral / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D016207:Cytokines