The effects of dyslipidaemia and cholesterol modulation on erythrocyte susceptibility to malaria parasite infection
Authors
Koch, Marion
Cegla, Jaimini
Jones, Ben
Lu, Yuning
Mallat, Ziad
Blagborough, Andrew M.
Angrisano, Fiona
Publication Date
2019-11-29Journal Title
Malaria Journal
Publisher
BioMed Central
Volume
18
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Koch, M., Cegla, J., Jones, B., Lu, Y., Mallat, Z., Blagborough, A. M., Angrisano, F., & et al. (2019). The effects of dyslipidaemia and cholesterol modulation on erythrocyte susceptibility to malaria parasite infection. Malaria Journal, 18 (1) https://doi.org/10.1186/s12936-019-3016-3
Abstract
Abstract: Background: Malaria disease commences when blood-stage parasites, called merozoites, invade human erythrocytes. Whilst the process of invasion is traditionally seen as being entirely merozoite-driven, emerging data suggests erythrocyte biophysical properties markedly influence invasion. Cholesterol is a major determinant of cell membrane biophysical properties demanding its interrogation as a potential mediator of resistance to merozoite invasion of the erythrocyte. Methods: Biophysical measurements of erythrocyte deformability by flicker spectroscopy were used to assess changes in erythrocyte bending modulus on forced integration of cholesterol and how these artificial changes affect invasion by human Plasmodium falciparum merozoites. To validate these observations in a natural context, either murine Plasmodium berghei or human Plasmodium falciparum merozoites were tested for their ability to invade erythrocytes from a hypercholesterolaemic mouse model or human clinical erythrocyte samples deriving from patients with a range of serum cholesterol concentrations, respectively. Results: Erythrocyte bending modulus (a measure of deformability) was shown to be markedly affected by artificial modulation of cholesterol content and negatively correlated with merozoite invasion efficiency. In an in vitro infection context, however, erythrocytes taken from hypercholesterolaemic mice or from human clinical samples with varying serum cholesterol levels showed little difference in their susceptibility to merozoite invasion. Explaining this, membrane cholesterol levels in both mouse and human hypercholesterolaemia erythrocytes were subsequently found to be no different from matched normal serum controls. Conclusions: Based on these observations, serum cholesterol does not appear to impact on erythrocyte susceptibility to merozoite entry. Indeed, no relationship between serum cholesterol and cholesterol content of the erythrocyte is apparent. This work, nonetheless, suggests that native polymorphisms which do affect membrane lipid composition would be expected to affect parasite entry. This supports investigation of erythrocyte biophysical properties in endemic settings, which may yet identify naturally protective lipid-related polymorphisms.
Keywords
Research, Plasmodium falciparum, Red blood cell, Host–parasite interactions, Flicker microscopy, Membrane biophysics, Merozoite
Sponsorship
Wellcome Trust (GB) (100993/Z/13/Z J.B.)
Medical Research Council (MR/K501281/1)
Identifiers
s12936-019-3016-3, 3016
External DOI: https://doi.org/10.1186/s12936-019-3016-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/313504
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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