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Dantu血型的红细胞张力可预防严重疟疾
2020-09-18 13:54

英国剑桥大学Julian C. Rayner、Pietro Cicuta以及英国伦敦帝国理工学院Thomas N. Williams研究组合作在研究中取得进展。他们发现红细胞张力可预防Dantu血型中的严重疟疾。 相关论文于2020年9月16日发表于国际顶尖学术期刊《自然》。

他们证明了Dantu对疟疾寄生虫恶性疟原虫裂殖子形式入侵红细胞(RBCs)能力的影响。他们发现Dantu与RBC表面蛋白种类的广泛变化有关,但是,出乎意料的是,抑制入侵与特定RBC-寄生虫受体-配体的相互作用无关。通过使用视频显微镜观察入侵,他们发现RBC张力与裂殖子入侵之间有很强的联系,并确定了一个张力阈值,即使在非Dantu RBC中也很少发生入侵。Dantu RBC的平均张力高于非Dantu RBC,这意味着更大的入侵抵抗力。

这些发现既为Dantu的保护作用提供了解释,又为在个体内部和个体之间发现的异种红细胞群体中恶性疟原虫入侵的效率不同提供了新的见解。

研究人员表示,疟疾已对人类基因组产生重大影响,在疟疾流行地区,已将许多保护性多态性(例如镰刀状细胞性状)选择为高频率。血型变异体Dantu对纯合个体的所有形式的严重疟疾提供74%的保护,这与镰状细胞性状所提供的保护程度相似,并且远比最好的疟疾疫苗所提供的保护程度高。但是,到目前为止,保护机制还不清楚。

附:英文原文

Title: Red blood cell tension protects against severe malaria in the Dantu blood group

Author: Silvia N. Kariuki, Alejandro Marin-Menendez, Viola Introini, Benjamin J. Ravenhill, Yen-Chun Lin, Alex Macharia, Johnstone Makale, Metrine Tendwa, Wilfred Nyamu, Jurij Kotar, Manuela Carrasquilla, J. Alexandra Rowe, Kirk Rockett, Dominic Kwiatkowski, Michael P. Weekes, Pietro Cicuta, Thomas N. Williams, Julian C. Rayner

Issue&Volume: 2020-09-16

Abstract: Malaria has had a major effect on the human genome, with many protective polymorphisms—such as the sickle-cell trait—having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3,4,5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC–parasite receptor–ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.

DOI: 10.1038/s41586-020-2726-6

Source: https://www.nature.com/articles/s41586-020-2726-6

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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