Nature:Dantu血型如何对抗疟疾?——研究发现高张力血细胞可以抵御寄生虫入侵

2020-09-21 Wellcome Trust Sanger Institute ScienceDaily

研究小组发现,拥有这种罕见Dantu血型的人红细胞表面张力更高,可以帮助他们抵御恶性疟原虫入侵,这项研究结果发表在(9月16日)的《自然》杂志上。

剑桥大学威康桑格研究所(Wellcome Sanger Institute)、剑桥大学(University of Cambridge)和KEMRI Wellcome Trust研究计划(KEMRI Wellcome Trust Research Programme)的科学家首次揭开了Dantu基因血液变体如何帮助抵御疟疾的秘密。研究小组发现,拥有这种罕见Dantu血型的人红细胞表面张力更高,可以帮助他们抵御恶性疟原虫入侵,这项研究结果发表在(9月16日)的《自然》杂志上。

DOI: 10.1038/s41586-020-2726-6

由于人类红细胞的表面张力随着年龄的增长而增加,所以科学家可能可以设计出能够模仿这种自然过程的药物来预防疟疾感染或减轻其严重程度。

疟疾现在仍然是一个主要的全球健康问题,估计每年造成435 000人死亡,其中61%发生于5岁以下儿童。其中恶性疟原虫是最致命的疟疾形式,在非洲尤其流行,2017年占非洲疟疾病例的99.7%,占全球疟疾死亡人数的93%。

2017年,研究人员发现,这种罕见的Dantu血型(仅在东非部分地区经常发现)在一定程度上对严重疟疾有保护作用。近期发表的这篇研究进一步探索了Dantu血型血细胞抵御虐接的原因。

研究中的红细胞样本来自肯尼亚基利菲的42名拥有Dantu基因1、2或0拷贝的健康儿童。研究人员使用了包括延时视频显微镜在内的多种工具,来观察寄生虫入侵细胞的能力,以确定红细胞受损的具体步骤。

对红细胞样本特征的分析表明,发生Dant变异的血细胞,细胞表面张力更高。在一定的张力下,疟原虫不再能够进入细胞,从而中止了它们的生命周期,并且阻止它们在血液中繁殖。

肯尼亚KEMRI Wellcome Trust研究项目的Silvia Kariuki博士说:“疟原虫利用一种特殊的‘锁钥’机制入侵人类红细胞,但结果发现答案基础得多。时机上,Dantu突变稍微增加了红细胞表面的张力。这就好比寄生虫还拿着锁的钥匙,但门变重了,无法打开。”

Dantu血型的红细胞表面表达了一种新的“嵌合”蛋白,并改变了其他表面蛋白质的平衡。在肯尼亚海岸的基利菲镇,有10%的人口拥有Dantu基因的一个拷贝,这种基因可以提供高达40%的疟疾保护。百分之一的人口有两种拷贝,提供高达70%的疟疾保护。相比之下,目前最好的疟疾疫苗仅可提供35%的保护。

研究人员认为,这项研究最重要的意义之一在于,人类红细胞的表面张力可在其约90天的寿命中逐渐增加。这意味着我们所有的红血球中有一部分天然地对疟原虫的感染有抵抗力,并且有可能开发出利用这一过程的药物。

剑桥大学的violaintorini博士说:“Dantu突变对于研究预防疟疾非常重要。红细胞膜只需要比平时稍微紧张一点就可以阻止疟原虫进入。开发一种能模拟这种‘紧张’的药物可能会是预防或治疗疟疾的简单有效的方法。当然,这需要在细胞张力的增加不产生意外的后果的情况下。”

原始出处:Silvia N. Kariuki, Alejandro Marin-Menendez, Viola Introini, et al. Red blood cell tension protects against severe malaria in the Dantu blood group. Nature, 2020; 

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    2021-08-30 liye789132251
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    2020-09-28 ms2000001021508404

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    2020-09-21 酷烨喋

    1

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