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

Published version
Peer-reviewed

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Authors

Egan, Elizabeth S 
Kanjee, Usheer 
Manzo, Jale 
Srinivasan, Ashwin 

Abstract

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.

Description

Keywords

3207 Medical Microbiology, 32 Biomedical and Clinical Sciences, 3202 Clinical Sciences, Infectious Diseases, Vector-Borne Diseases, Malaria, Rare Diseases, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Infection, 3 Good Health and Well Being

Journal Title

Commun Biol

Conference Name

Journal ISSN

2399-3642
2399-3642

Volume Title

1

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (108070/Z/15/Z)