Poster Presentation Lorne Infection and Immunity 2014

MICROPARTICLE MIRNA CONTENT AND FATE IN THE PATHOGENESIS OF EXPERIMENTAL CEREBRAL MALARIA  (#124)

Amy Cohen 1 , Fatima El-Assaad 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, fate and miRNA contents of MP during Plasmodium berghei-ANKA (PbA) infection of CM-susceptible (CM-S) and CM-resistant (CM-R) mice.

Upon infection, CM-S but not CM-R mice had raised plasma levels of MP. When adoptively transferred, fluorescent MP from CM-S mice into unfected or infected CM-R mice were quickly cleared from the circulation. Imaging showed arrested MP lining the endothelium of brain vessels of infected mice.

MP interact with, and modify, their target cells, potentially transferring their miRNA content. miRNA from MP purified from infected and uninfected CM-S mice were analysed using microarrays. There are 1966 murine miRNA present on the array, and when numbers of differentially expressed miRNA (against in-built control) were analysed: 410 and 365 were detected in infected and uninfected samples, respectively. From these, 243 were common while 167 and 122 were unique in infected and uninfected samples, respectively. Among those in common, 6 showed no change in expression and 25 a change greater than 4-fold in infected conditions. 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.

Together, these data highlight the importance of MP in the pathogenesis of neurological lesions through their role as a disease marker, their in vivo localization and the involvement of their content in controlling major biological pathways.   

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  2. 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: p. 140-151.
  3. 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(1): p. 295-302.