PNAS：儿童抵御疟疾感染的分子机制

近日，来自Sainte-Justine大学医学中心和蒙特利尔大学的研究者发现了一些新型基因，这些新型基因可以使得儿童的免疫系统对疟疾感染产生更为有效的反应。相关研究成果刊登在近日的国际杂志PNAS上。该文章的作者进行世界范围内的疟疾研究已经长达13年时间了。

疟疾是世界范围内的主要健康问题，每年有超过30亿人群处于高风险阶段，有成千上然的人因为疟疾感染而死亡。

本文研究中，研究者使用了一种不同于体外经典研究方法的新型方法，经典方法中，研究者是在实验室条件下分析细胞的基因组。然而在这项研究中，研究者使用体内的方法来分析来自西非贝宁共和国儿童的血样，这种新型方法可以使研究者清楚识别环境如何影响临床疾病的发病过程。

研究者使用了一种技术的创新结合方法，来评估儿童的遗传突变和其基因所表达的情况，这样一来，研究者不光可以检测儿童机体所发生的突变，也可以捕获在寄生虫存在的情况下，遗突变所影响的基因的开关效应。

理解基因信息如何影响儿童应对感染的能力，对于未来开发出低廉的检测方法非常重要，传染因子的正确诊断对于合适的疗法也非常关键。然而决定一个病人对于感染的易感性，可以使得研究者更加快速地研发出新型的抵御疾病的药物来治疗疾病。

编译自：Genetic make-up of children explains how they fight malaria infection

doi:10.1073/pnas.1204945109
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Evidence for additive and interaction effects of host genotype and infection in malaria

Youssef Idaghdoura, Jacklyn Quinlana, Jean-Philippe Gouleta, Joanne Berghoutb, Elias Gbehaa, Vanessa Bruata, Thibault de Malliarda, Jean-Christophe Greniera, Selma Gomezc,d, Philippe Grosb, Mohamed Chérif Rahimyd, Ambaliou Sannic, and Philip Awadallaa,1

The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8, C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children’s ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility.