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 regions 1 , 2 . The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals 3 – 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. The rare blood group Dantu is known to protect against severe malaria, and a mechanism is proposed here: Dantu red blood cells have a high membrane tension that prevents invasion by malaria parasites.

中文翻译：

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红细胞张力可预防丹徒血型的严重疟疾

疟疾对人类基因组产生了重大影响，许多保护性多态性（例如镰状细胞性状）在疟疾流行地区被选择为高频率 1 , 2 。Dantu 血型变体对纯合子个体 3 – 5 的所有形式的严重疟疾提供了 74% 的保护，与镰状细胞性状所提供的保护程度相似，并且比最好的疟疾疫苗所提供的保护程度要高得多。然而到目前为止，保护机制尚不清楚。在这里，我们展示了丹土对疟原虫恶性疟原虫裂殖子形式侵入红细胞（RBC）能力的影响。我们发现 Dantu 与红细胞表面蛋白质的广泛变化有关，但出乎意料的是，入侵的抑制与特定的红细胞 - 寄生虫受体 - 配体相互作用无关。通过使用视频显微镜跟踪入侵，我们发现红细胞张力和裂殖子入侵之间存在密切联系，并确定了一个张力阈值，高于该阈值入侵很少发生，即使在非 Dantu 红细胞中也是如此。丹徒红细胞比非丹徒红细胞具有更高的平均张力，这意味着更大比例的红细胞抵抗入侵。这些发现既解释了丹妥的保护作用，也为为什么恶性疟原虫入侵的效率在个体内部和个体之间发现的异质红细胞群体中可能存在差异提供了新的见解。已知罕见的丹徒血型可以预防严重的疟疾，这里提出了一种机制：丹徒红细胞具有高膜张力，可以防止疟疾寄生虫的入侵。