EXPLORING THE MIRNA CONTENT OF MICROPARTICLES AND THEIR POTENTIAL PATHOGENIC ROLE IN EXPERIMENTAL CEREBRAL MALARIA — University of Technology
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EXPLORING THE MIRNA CONTENT OF MICROPARTICLES AND THEIR POTENTIAL PATHOGENIC ROLE IN EXPERIMENTAL CEREBRAL MALARIA (14277)

Amy Cohen 1 , Anna Zinger 1 , Georges E.R. Grau 1 , Valery Combes 1
  1. University of Sydney, Camperdown, NSW, Australia

Microparticles (MP) are submicron vesicles involved in coagulation, inflammation and cell-cell communication. MP numbers are increased in cerebral malaria (CM) patients and in the corresponding murine model. In the latter, we showed that genetically or pharmacologically blocking MP release confers protection against CM, suggesting a role of MP in neuropathogenesis. Here, we evaluated the in vivo production and miRNA contents of MP during Plasmodium berghei-ANKA (PbA) infection of CM-susceptible (CM-S) and CM-resistant (CM-R) mice, and compare it to miRNA expression in the tissue of these mice.

miRNA in brain and heart tissue was analysed, comparing expression in uninfected mice, versus PbK-infected (non-encephalitogenic) or PbA-infected mice. Significant differences in expression were found in miRNA only between the brains of uninfected mice and mice with CM. However, the mechanism of pathogenesis of CM is still not fully understood, thus a comparison with microparticles is necessary. For the first time, it was confirmed that circulating microparticles contain miRNA. Thus, as MP interact with, and modify, their target cells, they potentially transfer their miRNA content. The miRNA content of microparticles from infected versus uninfected mice was analysed using microarrays. Many differentially expressed miRNA, and also miRNA unique to either infected or uninfected conditions were detected. Pathway analysis showed that these differentially expressed miRNA are mainly involved in the control of Th1 responses, apoptosis, homeostasis, and immunomodulation. These results are being further analysed using qRT-PCR to confirm changes following PbA infection.

These data suggest microparticles are not only severity markers but also active players in the pathogenesis of CM neurovascular lesions.

  1. Combes V, El-Assaad, F., Faille, D., Jambou, R., Hunt, N. H., Grau, G. E.R. Microvesiculation and cell interactions at the brain-endothelial interface in cerebral malaria pathogenesis. Progress in Neurobiology 2010;91:140-51.
  2. Coltel N, Combes, V., Wassmer, S. C., Chimini, G., Grau, G. E. R. Cell vesiculation and immunopathology: implications in cerebral malaria. Microbes and Infection 2006;8:2305-16.
  3. Penet M-F, Abou-Hamdan, M., Coltel, N., Cornille, E., Grau, G. E. R., de Reggi, M., Gharib, B. Protection against cerebral malaria by the low-molecular-weight thiol pantethine. PNAS 2008;105:1321-6.
  4. Combes V, Coltel, N., Albert, M., van Eck, M., Raymond, C., Juhan-Vague, I., Grau, G. E. R., Chimini, G. ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology. American Journal of Pathology 2005;166:295-302.
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