Transgenic Plasmodium chabaudi for analysis of host/parasite interactions

用GFP或荧光素酶转基因寄生虫在伯氏疟原虫模型中评价宿主寄生虫相互作用已取得重大进展。尽管夏氏疟原虫被认为是比伯氏疟原虫更好的恶性疟原虫模型，但迄今为止还没有操作夏氏疟原虫基因组的方法。本申请的目的是建立GFP-荧光素酶转基因夏氏毕赤酵母。然后，这些寄生虫将用于分析野生型但非光敏素β受体缺陷（LTβR-/-）小鼠中从脾脏中排除寄生虫红细胞（脾脏“关闭”）对寄生虫隔离及其与吞噬细胞相互作用的影响。转基因寄生虫还将用于通过野生型或LTβR-/-小鼠传代来选择抗原性新寄生虫变体。这些实验将揭示脾脏通道是否对寄生虫施加选择性免疫压力，以及抗原变异引起的免疫逃避是否抵消了这种压力。此外，结果将显示抗原性不同的寄生虫是否表现出不同的隔离模式。

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.