| Summary: | Currently there are 3.3 billion people world -wide at risk of contracting malaria with the species Plasmodium falciparum being responsible for around 1 million deaths annually. P. Falciparum causes a symptom known as cerebral malaria (CM) which, if not treated quickly results in an unrousable coma which can lead to death with in 24-72 hours. With the use of mouse malaria models, the causes of CM are becoming clearer and currently it is understood to be caused by the sequestration of parasitized red blood cells, leukocytes and plate lets with in the microvasculature within the cerebral cortex. This sequestration is linked to inflammation with IFNy and TNFa being key initiators in promoting CM pathology. Although platelets sequester with in the cerebral cortex and malaria is usually accompanied by thrombocytopenia; however, a link between platelets and pathology has never been fully established. The data in this study demonstrates that an increase in parasite biomass is thrombocytopenia and that both parasitaemia and thrombocytopenia are linked to pathology in malaria. The data in this report also shows that mice are rescued from associated malaria pathology when platelets are depleted or inhibited. Analysing splenic leukocyte populations, our data demonstrated that the source of the increase in plasma concentrations of IL-IO and IFNy in P. berghei-infected platelet-depleted mice as shown by Van der Heyde et al. is possibly down to the increase in activated IFNy-expressing Th1 cells. Platelet depletion or platelet antagonist treatment in P. berghei infected also results in an increased population of IL-lO-producing Th2 and self-limiting IL-10-producing Thl cells that have been shown to be crucial in preventing immunopathology. This increase in the expansion of Thl and Th2 populations in response to P. berghei infection is not mediated by the antigen presenting cell populations, as they population and their maturity appears to be un-affected by either platelet depletion or platelet inhibition.
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