Poster Presentation First Malaria World Congress 2018

Investigating malaria-specific T cells responses in the brain of mice with ECM   (#287)

Nazanin Ghazanfari 1 , Scott Mueller 1 , William Heath 1
  1. Peter Doherty Institute/The University of Melbourne, Melbourne, VICTORIA, Australia

Human cerebral malaria (HCM) is a severe neurological complication caused by the malaria parasite Plasmodium falciparum that results in thousands of deaths each year. The precise mechanisms underlying cerebral malaria pathogenesis are not entirely understood. Methods: To investigate the pathogenesis of cerebral malaria, we use the well-established animal model of experimental cerebral malaria (ECM). We used intravital microscopy to image the brains in live animals undergoing malarial infection. We injected CB57Bl/6 mice with antigen-specific PbT-I CD8+ T cells or antigen-specific PbT-II CD4+ T cells a day before infection with Plasmodium berghei ANKA (PbA) blood-stage parasites. Two-photon laser scanning microscopy was performed through a cover-slipped cranial window, which allows observation of the immune responses occurring in the brain in real time. Results: CB57Bl/6 mice infected with PbA showed symptoms of cerebral malaria 6-7 days after infection. PbT-I and PbT-II T cells were both present in the brain blood vessels from day 6 post-infection and entered the brain parenchyma by day 7. Flow cytometric analysis after intravascular Ab labelling confirmed the accumulation of transgenic T cells as well as endogenous CD4+ and CD8+ T cells within the brain parenchyma of both acutely infected and long-term cured mice. The presence of PbT-I T cells in the brain of cured mice was also confirmed by intravital microscopy. Conclusion: These results suggest that both CD4+ and CD8+ T cells infiltrate the brain during ECM, with some cells forming long-term memory in this site. They also raise the possibility that infiltration of CD4+ T cells into the brain parenchyma may contribute to cerebral immunopathology.