Investigation of plasma-derived lipidome profiles in experimental cerebral malaria in a mouse model study

Cerebral malaria (CM), a fatal complication of Plasmodium infection that affects children especially under the age of five in sub-Saharan Africa and adults in South-East Asia, results from incompletely understood pathogenetic mechanisms. Increased release of circulating miRNA, proteins, lipids and extracellular vesicles have been found in CM patients and experimental mouse models. We compared lipid profiles derived from the plasma of CBA mice infected with P. berghei ANKA (PbA), which causes CM, to those from P. yoelii (Py), which does not. Here, we show that plasma microvesicles (MVs) produced at the time of CM differed dramatically from those of non-CM mice, despite identical levels of parasitaemia. Using high-resolution LCMS, we identified over 300 lipid species within 12 lipid classes. Total lysophosphatidylethanolamine (LPE) levels were significantly lower in PbA infection compared to uninfected mice, while they were unchanged in Py, and lysophosphatidylcholine (LPC) was more significantly reduced in PbA mice compared to the other two groups. These results suggest that experimental CM is characterised by specific changes in lipid composition of circulating MV, pointing towards triglycerides (TG), especially docosahexaenoic acid (DHA 22:6) containing species, phosphatidylethanolamine (PE), LPC, LPE, and diacylglycerol (DG) as potentially important players in CM pathogenesis.