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Updated: May 11, 2026
In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging
Published on: June 8, 2017
Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria
Shanshan W Howland1, Chek Meng Poh, Sin Yee Gun
1Singapore Immunology Network, Agency for Science, Technology and Research A*STAR, Singapore, Singapore.
Abstract:
Cerebral malaria is a devastating complication of Plasmodium falciparum infection. Its pathogenesis is complex, involving both parasite- and immune-mediated events. CD8(+) T cells play an effector role in murine experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. We have identified a highly immunogenic CD8 epitope in glideosome-associated protein 50 that is conserved across rodent malaria species. Epitope-specific CD8(+) T cells are induced during PbA infection, migrating to the brain just before neurological signs manifest. They are functional, cytotoxic and can damage the blood-brain barrier in vivo. Such CD8(+) T cells are also found in the brain during infection with parasite strains/species that do not induce neuropathology. We demonstrate here that PbA infection causes brain microvessels to cross-present parasite antigen, while non-ECM-causing parasites do not. Further, treatment with fast-acting anti-malarial drugs before the onset of ECM reduces parasite load and thus antigen presentation in the brain, preventing ECM death. Thus our data suggest that combined therapies targeting both the parasite and host antigen-presenting cells may improve the outcome of CM patients.
Insights
CD8(+) T cells target Plasmodium falciparum in cerebral malaria (CM). Early anti-malarial treatment and targeting antigen presentation may prevent this severe complication.
Area of Science:
- Immunology
- Infectious Diseases
- Neuroscience
Background:
- Cerebral malaria (CM) is a severe Plasmodium falciparum complication.
- Pathogenesis involves parasite and immune factors.
- CD8(+) T cells are effectors in experimental cerebral malaria (ECM).
Purpose of the Study:
- Identify CD8(+) T cell epitopes in Plasmodium berghei ANKA (PbA).
- Investigate CD8(+) T cell migration and function in the brain during ECM.
- Determine the role of antigen presentation in ECM pathogenesis.
Main Methods:
- Identified a CD8 epitope in glideosome-associated protein 50.
- Induced epitope-specific CD8(+) T cells in PbA-infected mice.
- Analyzed T cell infiltration and function in the brain.
- Examined antigen cross-presentation by brain microvessels.
Main Results:
- Epitope-specific CD8(+) T cells are induced and migrate to the brain before neurological signs.
- These T cells are cytotoxic and can damage the blood-brain barrier.
- PbA infection induces antigen cross-presentation by brain microvessels, unlike non-ECM parasites.
- Early anti-malarial drug treatment reduces parasite load, antigen presentation, and prevents ECM death.
Conclusions:
- CD8(+) T cells play a critical role in ECM pathogenesis.
- Brain microvessel cross-presentation of parasite antigen is crucial for ECM.
- Combined therapies targeting parasites and host antigen-presenting cells may improve CM outcomes.
