Presenter: Brittany Riggle, National Institutes of Health, USA
From the EMBL Conference: BioMalPar XVI: Biology and Pathology of the Malaria Parasite
18 - 19 May 2020, Virtual
ABSTRACT
Infection with mosquito-transmitted Plasmodium falciparum parasites causes malaria and is disproportionately fatal in young children in Africa. Malaria-associated fatalities are overwhelmingly caused by cerebral malaria, a severe manifestation that does not adequately respond to intravenous antimalarial therapy. The abundance of infected red blood cells that accumulate in the cerebral vasculature of many patients has led to the belief that these brain-sequestered cells are causative players in severe disease. However, mouse models of cerebral malaria robustly implicate CD8+ T cells in pathogenesis, but lack of human corroboration has diminished interest in identifying therapeutic targets. We performed multiplex immunohistochemistry in post-mortem brain samples from children with or without cerebral malaria and with known HIV status. Cerebral malaria diagnosis was associated with elevated numbers of CD3+CD8+ T cells engaging the cerebrovasculature. HIV co-infection further increases CD3+CD8+ T cell engagement as well as enhanced distribution into the cerebral perivasculature. These data provide a rationale for investigating CD3+CD8+ T cells as the target of an adjunctive therapy for cerebral malaria.
