Mensah-Brown Henrietta E, Amoako Nicholas, Abugri James, Stewart Lindsay B, Agongo Godfred, Dickson Emmanuel K, Ofori Michael F, Stoute José A, Conway David J, Awandare Gordon A
West African Center for Cell Biology of Infectious Pathogens Department of Biochemistry, Cell and Molecular Biology.
Kintampo Health Research Center.
J Infect Dis. 2015 Oct 15;212(8):1288-97. doi: 10.1093/infdis/jiv207. Epub 2015 Apr 2.
Plasmodium falciparum invades human erythrocytes by using an array of ligands that interact with several receptors, including sialic acid (SA), complement receptor 1 (CR1), and basigin. We hypothesized that in malaria-endemic areas, parasites vary invasion pathways under immune pressure. Therefore, invasion mechanisms of clinical isolates collected from 3 zones of Ghana with different levels of endemicity (from lowest to highest, Accra, Navrongo, and Kintampo) were compared using standardized methods.
Blood samples were collected from children aged 2-14 years in whom malaria was diagnosed, and erythrocyte invasion phenotypes were determined using the enzymes neuraminidase, chymotrypsin, and trypsin, which differentially cleave receptors from the erythrocyte surface. In addition, antibodies against CR1 and basigin were used to determine the contributions of these receptors to invasion. Gene expression levels of P. falciparum invasion ligands were also examined.
The parasites generally expressed SA-independent invasion phenotypes across the malaria-endemic areas, with parasites from Kintampo showing the highest invasion rates in neuraminidase-treated erythrocytes. CR1 was a major mediator of SA-independent invasion, while basigin was essential for both SA-dependent and SA-independent invasion mechanisms. Furthermore, expression of the basigin ligand PfRh5 was the best predictor of donor parasitemia.
Erythrocyte invasion phenotypes expressed by P. falciparum are influenced by endemicity levels, and the PfRh5-basigin pathway is a potential vaccine target.
恶性疟原虫通过一系列与多种受体相互作用的配体侵入人类红细胞，这些受体包括唾液酸（SA）、补体受体1（CR1）和基底膜蛋白。我们推测，在疟疾流行地区，寄生虫在免疫压力下会改变侵入途径。因此，我们使用标准化方法比较了从加纳3个流行程度不同（从低到高依次为阿克拉、纳瓦龙戈和金坦波）的地区收集的临床分离株的侵入机制。
采集2至14岁被诊断为疟疾的儿童的血样，使用神经氨酸酶、胰凝乳蛋白酶和胰蛋白酶等酶来确定红细胞侵入表型，这些酶可不同程度地切割红细胞表面的受体。此外，使用针对CR1和基底膜蛋白的抗体来确定这些受体对侵入的作用。还检测了恶性疟原虫侵入配体的基因表达水平。
在整个疟疾流行地区，寄生虫通常表现出不依赖SA的侵入表型，来自金坦波的寄生虫在经神经氨酸酶处理的红细胞中显示出最高的侵入率。CR1是不依赖SA侵入的主要介质，而基底膜蛋白对于依赖SA和不依赖SA的侵入机制均至关重要。此外，基底膜蛋白配体PfRh5的表达是供体寄生虫血症的最佳预测指标。
恶性疟原虫表达的红细胞侵入表型受流行程度影响，PfRh5-基底膜蛋白途径是一个潜在的疫苗靶点。
