Children are highly susceptible to clinical malaria, and in regions where malaria is endemic, their immune systems must face successive encounters with Plasmodium falciparum parasites before they develop immunity, first against severe disease and later against uncomplicated malaria. Understanding cellular and molecular interactions between host and parasites during an infection could provide insights into the processes underlying this gradual acquisition of immunity, as well as to how parasites adapt to infect hosts that are successively more malaria experienced. Here, we describe methods to analyze the host and parasite gene expression profiles generated simultaneously from blood samples collected from five consecutive symptomatic P. falciparum infections in three Malian children. We show that the data generated enable statistical assessment of the proportions of (i) each white blood cell subset and (ii) the parasite developmental stages, as well as investigations of host-parasite gene coexpression. We also use the sequences generated to analyze allelic variations in transcribed regions and determine the complexity of each infection. While limited by the modest sample size, our analyses suggest that host gene expression profiles primarily clustered by individual, while the parasite gene expression profiles seemed to differentiate early from late infections. Overall, this study provides a solid framework to examine the mechanisms underlying acquisition of immunity to malaria infections using whole-blood transcriptome sequencing (RNA-seq).

中文翻译：

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幼儿期恶性疟原虫感染后宿主和寄生虫转录组的变化。

儿童极易感染临床疟疾，在疟疾流行地区，他们的免疫系统必须先连续遇到恶性疟原虫寄生虫，然后才能形成免疫力，首先要抵抗严重的疾病，然后才是对复杂的疟疾的抵抗。了解感染过程中宿主与寄生虫之间的细胞和分子相互作用可以提供洞悉这种逐渐获得免疫力的过程，以及寄生虫如何适应感染疟疾的宿主的洞见。在这里，我们描述了分析从连续五个有症状的恶性疟原虫采集的血液样本中同时产生的宿主和寄生虫基因表达谱的方法三个马里儿童感染。我们表明生成的数据能够统计评估（i）每个白细胞子集和（ii）寄生虫发育阶段的比例，以及对宿主-寄生虫基因共表达的研究。我们还使用生成的序列来分析转录区域中的等位基因变异，并确定每种感染的复杂性。尽管受到样本量的限制，但我们的分析表明宿主基因表达谱主要由个体聚集，而寄生虫基因表达谱似乎可以早期感染与晚期感染区分开。总体而言，这项研究提供了一个坚实的框架，可用于研究使用全血转录组测序（RNA-seq）对获得疟疾感染的免疫力的潜在机制。