TY - JOUR T1 - The effects of dyslipidaemia and cholesterol modulation on erythrocyte susceptibility to malaria parasite infection JF - bioRxiv DO - 10.1101/630251 SP - 630251 AU - Marion Koch AU - Jaimini Cegla AU - Ben Jones AU - Yuning Lu AU - Ziad Mallat AU - Andrew Blagborough AU - Fiona Angrisano AU - Jake Baum Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/15/630251.abstract N2 - Malaria disease commences when blood-stage parasites, called merozoites, invade human red blood cells (RBCs). Whilst the process of invasion is traditionally seen as being entirely merozoite-driven, emerging data suggests RBC biophysical properties markedly influence invasion. Cholesterol is a major determinant of cell membrane biophysical properties. We set out to assess whether cholesterol content in the RBC membrane affects susceptibility to merozoite invasion. Here we demonstrate that RBC bending modulus (a measure of deformability) is markedly affected by artificial modulation of cholesterol content and negatively correlated with merozoite invasion efficiency. Contextualising this observation, we tested a mouse model of hypercholesterolemia and human clinical samples from patients with a range of serum cholesterol concentrations for parasite susceptibility. Hypercholesterolaemia in both human and murine subjects had little effect merozoite invasion efficiency. Furthermore, on testing, RBC cholesterol content in both murine and human hypercholesterolaemia settings was found to be unchanged from normal controls. Serum cholesterol is, therefore, unlikely to impact on RBC susceptibility to merozoite entry. Our work, however, suggests that native polymorphisms that affect RBC membrane lipid composition would be expected to affect parasite entry. This supports investigation of RBC biophysical properties in endemic settings, which may yet identify naturally protective lipid-related polymorphisms. ER -