Variation in Plasmodium falciparum Erythrocyte Invasion Phenotypes and Merozoite Ligand Gene Expression across Different Populations in Areas of Malaria Endemicity
Variation in Plasmodium falciparum Erythrocyte Invasion Phenotypes and Merozoite Ligand Gene Expression across Different Populations in Areas of Malaria Endemicity
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DOI：
10.1128/iai.03009-14
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发表时间：
2015-06-01
影响因子：
3.1
通讯作者：
Conway, David J.
中科院分区：
文献类型：
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作者：
Bowyer, Paul W.;Stewart, Lindsay B.;Conway, David J.
恶性疟原虫裂殖子利用多种替代红细胞受体进行入侵，并可变地表达由红细胞结合抗原（eba）和网织红细胞结合样同源物（Rh）基因家族编码的同源配体。先前对流行地区单一种群的寄生虫进行的分析揭示了广泛的入侵表型和表达谱，尽管不同研究的比较因使用不同的方案而受到限制。为了在人群内部和人群之间进行直接比较，来自三个不同西非流行地区（加纳、几内亚和塞内加尔）的临床分离株被冷冻保存，并在单个实验室解冻后离体培养，以测定用影响受体亚群的酶预处理的目标红细胞的侵袭情况。 67 个分离株的完整侵袭测定数据显示，通过神经氨酸酶处理（总体平均值，40.6% 抑制）或胰蛋白酶处理（总体平均值，83.3% 抑制）测量的广泛表型，群体之间没有差异。胰凝乳蛋白酶治疗的效果（总体平均值，79.2% 抑制）显示出不同人群的异质性（Kruskall-Wallis P = 0.023），尽管每个人群都看到了完整的表型范围。获得了 37 个分离株的一组 8 个入侵配体基因（eba175、eba140、eba181、Rh1、Rh2a、Rh2b、Rh4 和 Rh5）的裂殖期转录数据，显示每个群体中相似的变异范围，除了来自加纳的寄生虫中的 eba175 水平往往高于来自塞内加尔的寄生虫（而来自塞内加尔的寄生虫中的 eba181 和 Rh2b 水平较低）。来自加纳的寄生虫）。每个当地种群中的入侵表型和基因表达存在广泛的多样性，并且它们之间的差异很小，这与免疫选择维持寄生虫变异的假设是一致的。
Plasmodium falciparum merozoites use diverse alternative erythrocyte receptors for invasion and variably express cognate ligands encoded by the erythrocyte binding antigen (eba) and reticulocyte binding-like homologue (Rh) gene families. Previous analyses conducted on parasites from single populations in areas of endemicity revealed a wide spectrum of invasion phenotypes and expression profiles, although comparisons across studies have been limited by the use of different protocols. For direct comparisons within and among populations, clinical isolates from three different West African sites of endemicity (in Ghana, Guinea, and Senegal) were cryopreserved and cultured ex vivo after thawing in a single laboratory to assay invasion of target erythrocytes pretreated with enzymes affecting receptor subsets. Complete invasion assay data from 67 isolates showed no differences among the populations in the broad range of phenotypes measured by neuraminidase treatment (overall mean, 40.6% inhibition) or trypsin treatment (overall mean, 83.3% inhibition). The effects of chymotrypsin treatment (overall mean, 79.2% inhibition) showed heterogeneity across populations (Kruskall-Wallis P = 0.023), although the full phenotypic range was seen in each. Schizont-stage transcript data for a panel of 8 invasion ligand genes (eba175, eba140, eba181, Rh1, Rh2a, Rh2b, Rh4, and Rh5) were obtained for 37 isolates, showing similar ranges of variation in each population except that eba175 levels tended to be higher in parasites from Ghana than in those from Senegal (whereas levels of eba181 and Rh2b were lower in parasites from Ghana). The broad diversity in invasion phenotypes and gene expression seen within each local population, with minimal differences among them, is consistent with a hypothesis of immune selection maintaining parasite variation.