Poster Presentation Australasian Extracellular Vesicles Conference 2020

Lipidomics profiles of plasma microvesicles differ in experimental cerebral malaria, compared to malaria without neurological complications (#51)

Amani Batarseh 1 , Elham Hosseini Beheshti 2 , Fatemeh Vafaee 3 , Alex Chen 4 , Amy Cohen 2 , Annette Juillard 2 , Nicholas Henri Hunt 5 , Michael Mariani 6 , Todd Mitchell 7 , Georges Emile Raymond Grau 2
  1. BCAL Diagnostics, Eveleigh, NSW, Australia
  2. Vascular Immunology Unit, Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia, School of Medicine, University of Sydney, Sydney, NSW, Australia
  3. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
  4. LC-MS Engineer, Thermo Fisher Scientific, Scoresby, NSW, Australia
  5. Molecular Immunopathology Unit, Bosch Institute, University of Sydney, Sydney, NSW, Australia, Sydeny, NSW, Australia
  6. Thermo Fisher Scientific, North Ryde, NSW, Australia, North Ryde, NSW, Australia
  7. School of Medicine, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, NSW, Australia

Cerebral malaria (CM), a fatal complication of Plasmodium infection affecting children in sub-Saharan Africa and adults in South-East Asia, results from incompletely understood pathogenetic mechanisms, which include sequestration of infected erythrocytes, cytokine overproduction, accumulation of inflammatory cells, and excessive release of microvesicles (MV). Plasma MV levels are elevated in CM patients and in the experimental mouse model. Here, MV lipidomics profile was studied in relation to the development of cerebral complications.

Plasma MV were enriched using differential centrifugation. Lipids were extracted according to Matyash et al. 2008, loaded on a C30 Acclaim column using a Vanquish liquid chromatography (LC) system and analysed using a Fusion mass spectrometer (MS). LipidSearch software was used for lipid species annotation and quantification.

We compared lipid profiles in circulating MV purified from CBA mice with P. berghei ANKA (PbA), which causes CM, to those from P. yoelii (Py), which does not. Plasma MV produced at the time of CM dramatically differed from those from non-CM mice, in spite of identical levels of parasitaemia: using high-resolution LCMS, we identified over 300 lipid species within 12 lipid classes. Total phosphatidylethanolamine (PE) levels were significantly higher in MV from PbA mice compared to those from uninfected control and Py. Using fragmentation MS, we identified that this PE increase is due at least in part to PE (16:0_22:6), PE (18:0_22:6) and PE (18:1_22:6) species identified in PbA vs Py and uninfected control. A possible role for DHA 22:6 containing lipids requires additional investigation. Conversely total Lysophosphatidylethanolamine (LPE) were significantly lower in PbA compared to uninfected mice, while they were unchanged in Py MV. Total phosphatidylserine (PS), Diglycerides (DG) and Hex1Cer total lipids were significantly higher in both PbA and Py compared to uninfected control.

These results suggest, for the time, that experimental CM is characterised by specific changes in lipid composition of circulating MV, pointing towards PE subsets, LPC, LPE, Hex1Cer and DG as potential important players in CM pathogenesis.