Activated Brain Endothelial Cells Cross-Present Malaria Antigen

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Cerebral malaria accounts for most of the deaths caused by Plasmodium infection. In the mouse model of cerebral malaria, CD8+ T cells are known to be the effector cells responsible for lethal neuropathology, but it was not clear how they disrupted the blood-brain barrier. Here, we show that brain endothelial cells cross-present parasite antigen at the onset of pathology, hence allowing recognition by parasite-specific cytotoxic T lymphocytes. This process did not occur in mice lacking IFNγ, whereas TNFα and LTα were dispensable. The proposed mechanism of pathogenesis was recapitulated in vitro: IFNγ-stimulated primary mouse brain endothelial cells cultured with parasite-infected red blood cells were subsequently killed by CD8+ T cells isolated from an infected mouse. The murine endothelial cells primarily phagocytose not infected red blood cells but instead merozoites, the form of the parasite that infects red blood cells. We show also that human brain endothelial cells phagocytose P. falciparum merozoites in vitro, suggesting that our findings with the mouse model may be relevant to human disease. Strategies to interfere with merozoite phagocytosis or antigen processing by endothelial cells may prove useful for treating cerebral malaria.

Vyšlo v časopise: Activated Brain Endothelial Cells Cross-Present Malaria Antigen. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004963
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004963

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