Transgenic Plasmodium chabaudi for analysis of host/parasite interactions

点击翻译按钮获取中文摘要

Significant progress in evaluation of host parasite interactions in the Plasmodium berghei model has been achieved with GFP or luciferase transgenic parasites. Although Plasmodium chabaudi is considered to be a much better model for Plasmodium falciparum than P. berghei, methods for manipulation of the P. chabaudi genome are hitherto not available. The aim of this application is to establish GFP-luciferase transgenic P. chabaudi. These parasites will then be used to analyze effects of exclusion of parasitized erythrocytes from the spleen (spleen ‘closing’) in wild-type but not lymphotoxin β receptor-deficient (LTβR-/-) mice on parasite sequestration and their interaction with phagocytic cells. The transgenic parasites will also be used to select antigenically new parasite variants by passage through wild-type or LTβR-/- mice. These experiments will reveal if spleen passage exerts a selective immune pressure on the parasite and if immune evasion by antigenic variation counteracts this pressure. Moreover, the results will show whether antigenically different parasites exhibit different sequestration patterns.