The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion.
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Authors
Lin, Yen-Chun
Smith, Adrian L
Jean, Letitia
Brewin, John N
Rees, David C
Publication Date
2022-05-27Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
12
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Introini, V., Marin-Menendez, A., Nettesheim, G., Lin, Y., Kariuki, S. N., Smith, A. L., Jean, L., et al. (2022). The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion.. Sci Rep, 12 (1) https://doi.org/10.1038/s41598-022-12060-4
Abstract
Malaria parasites such as Plasmodium falciparum have exerted formidable selective pressures on the human genome. Of the human genetic variants associated with malaria protection, beta thalassaemia (a haemoglobinopathy) was the earliest to be associated with malaria prevalence. However, the malaria protective properties of beta thalassaemic erythrocytes remain unclear. Here we studied the mechanics and surface protein expression of beta thalassaemia heterozygous erythrocytes, measured their susceptibility to P. falciparum invasion, and calculated the energy required for merozoites to invade them. We found invasion-relevant differences in beta thalassaemic cells versus matched controls, specifically: elevated membrane tension, reduced bending modulus, and higher levels of expression of the major invasion receptor basigin. However, these differences acted in opposition to each other with respect to their likely impact on invasion, and overall we did not observe beta thalassaemic cells to have lower P. falciparum invasion efficiency for any of the strains tested.
Keywords
Erythrocyte Membrane, Heterozygote, Humans, Malaria, Malaria, Falciparum, Plasmodium falciparum, beta-Thalassemia
Sponsorship
Wellcome Trust Junior Interdisciplinary Fellowship (Wellcome 20485/Z/16/Z)
Wellcome Trust (20485/Z/16/Z, 220266/Z/20/Z, 206194/Z/17/Z)
Identifiers
35624125, PMC9142571
External DOI: https://doi.org/10.1038/s41598-022-12060-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338576
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