Erythrocytes lacking the Langereis blood group protein ABCB6 are resistant to the malaria parasite Plasmodium falciparum.

Erythrocytes lacking the Langereis blood group protein ABCB6 are resistant to the malaria parasite Plasmodium falciparum.
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DOI:
10.1038/s42003-018-0046-2
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发表时间:
2018
影响因子:
5.9
通讯作者:
Duraisingh MT
Duraisingh MT
中科院分区:
生物学2区
文献类型:
--
作者:
Egan ES;Weekes MP;Kanjee U;Manzo J;Srinivasan A;Lomas-Francis C;Westhoff C;Takahashi J;Tanaka M;Watanabe S;Brugnara C;Gygi SP;Tani Y;Duraisingh MT

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atp结合盒转运体ABCB6最近被发现编码兰格氏(Lan)血型抗原。少数个体无症状,ABCB6在成熟红细胞中的功能尚不清楚。在这里,我们评估了ABCB6作为恶性疟原虫在红细胞侵袭过程中的宿主因子。我们发现Lan null红细胞对恶性疟原虫的侵袭具有高度的抗性,以一种超越菌株的方式。虽然Lan null和Jr(a-)红细胞都含有过量的卟啉,但只有Lan null红细胞表现出恶性疟原虫侵袭缺陷。此外,人畜共患寄生虫诺氏疟原虫入侵蓝细胞和对照细胞的效率相似,这表明ABCB6可能通过物种特异性分子相互作用介导恶性疟原虫的入侵。利用串联质量标签的蛋白质组学,我们发现Lan null和对照细胞之间膜蛋白的唯一一致差异是缺乏ABCB6。我们的研究结果表明,一种新发现的自然发生的血型变异与恶性疟原虫的耐药性有关。Elizabeth Egan及其同事证明,宿主ATP结合盒转运蛋白ABCB6(编码朗格氏血型抗原)促进疟原虫恶性疟原虫入侵红细胞。这项研究表明,无症状的朗格氏阳性个体可能更容易受到疟疾的保护。
The ATP-binding cassette transporter ABCB6 was recently discovered to encode the Langereis (Lan) blood group antigen. Lan null individuals are asymptomatic, and the function of ABCB6 in mature erythrocytes is not understood. Here, we assessed ABCB6 as a host factor for Plasmodium falciparum malaria parasites during erythrocyte invasion. We show that Lan null erythrocytes are highly resistant to invasion by P. falciparum, in a strain-transcendent manner. Although both Lan null and Jr(a-) erythrocytes harbor excess porphyrin, only Lan null erythrocytes exhibit a P. falciparum invasion defect. Further, the zoonotic parasite P. knowlesi invades Lan null and control cells with similar efficiency, suggesting that ABCB6 may mediate P. falciparum invasion through species-specific molecular interactions. Using tandem mass tag-based proteomics, we find that the only consistent difference in membrane proteins between Lan null and control cells is absence of ABCB6. Our results demonstrate that a newly identified naturally occurring blood group variant is associated with resistance to Plasmodium falciparum. Elizabeth Egan and colleagues demonstrate that host ATP binding cassette transporter ABCB6, which encodes the Langereis blood group antigen, promotes erythrocyte invasion by the malaria parasite Plasmodium falciparum. This study suggests that asymptomatic Langereis null individuals may be better protected from malaria.
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