Malaria Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
Ferrier Research Institute, Chemical Biology Laboratory, Kelburn Parade, Victoria University of Wellington, PO Box 600, Wellington, 6140, New Zealand.
Sci Rep. 2018 May 25;8(1):8133. doi: 10.1038/s41598-018-26559-2.
Malaria has been one of the strongest selective forces on the human genome. The increased frequency of haemoglobinopathies, as well as numerous other blood groups, in malaria endemic regions is commonly attributed to a protective effect of these alleles against malaria. In the majority of these cases however there have been no systematic functional studies to test protective mechanisms, in large part because most host-parasite interaction assays are not quantitative or scalable. We describe the development of an erythrocyte preference assay which uses differential labelling with fluorescent dyes to distinguish invasion into four different erythrocyte populations which are all co-incubated with a single Plasmodium falciparum parasite culture. Testing this assay on erythrocytes across the ABO blood system from forty independent donors reveals for the first time that P. falciparum parasites preferentially invade group O over Group A erythrocytes. This runs counter to the known protective effect of group O against severe malaria, but emphasises the complexities of host-pathogen interactions, and the need for highly quantitative and scalable assays to systematically explore them.
疟疾一直是人类基因组中最强的选择因素之一。在疟疾流行地区，血红蛋白病以及许多其他血型的频率增加通常归因于这些等位基因对疟疾的保护作用。然而，在大多数情况下，没有进行系统的功能研究来测试保护机制，这在很大程度上是因为大多数宿主-寄生虫相互作用的测定方法不是定量或可扩展的。我们描述了一种红细胞偏好测定法的开发，该测定法使用荧光染料的差异标记来区分四种不同的红细胞群体的入侵，所有这些群体都与单一的恶性疟原虫寄生虫培养物共孵育。在来自 40 个独立供体的 ABO 血型系统的红细胞上测试该测定法，首次表明恶性疟原虫寄生虫优先入侵 O 组红细胞而不是 A 组红细胞。这与 O 组对严重疟疾的已知保护作用背道而驰，但强调了宿主-病原体相互作用的复杂性，以及需要高度定量和可扩展的测定法来系统地探索这些相互作用。
