Microvesicles (MV) are submicron vesicles involved in coagulation, inflammation and cell-cell communication. MV numbers increase in cerebral malaria (CM) patients and in the murine model, where blocking MV release protects against brain pathology, suggesting a role of MV in neuropathogenesis.
For the first time, miRNA cargo of MV during Plasmodium berghei ANKA and P. yoelii (non-CM) infection was evaluated. The miRNA content of MV from CM versus non-infected (NI) mice was analysed using microarrays. miRNA of interest were further analysed using qRT-PCR to confirm changes in CM compared with NI and non-CM mice, and to compare miRNA expression in MV with plasma and brain tissue.
We identified >400 miRNA in each category. 350 of these were differentially expressed, 15 significantly so (p<0.05). Following infection, miRNA encapsulated in plasma MV and expressed in the brain tissue were altered in mice with CM, coinciding with the onset of the neurological syndrome. Particularly, miR-146a and miR-193b were found to be significantly dysregulated in plasma MV from CM mice; these miRNA interact with mRNA targets to affect the downstream production of proteins involved in apoptosis, cytokine regulation and the recruitment of inflammatory cells.
Together, these data suggest the potential of miRNA – either MV-encapsulated or expressed in brain tissue – to play a regulatory role in the pathogenesis of experimental CM. Furthermore, evidence is provided that MV are not only severity markers but also active players in the pathogenesis of CM neurovascular lesions and in the systemic spread of CM.