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[Pathogenesis of cerebral malaria: facts and hypotheses]
S C Wassmer1, N Coltel, V Combes
1L'Unité de Parasitologie expérimentale, Laboratoire d'Immunopathologie, Faculté de Médecine, EA3282 UnivMed-IPP-IMTSSA, Marseille, France.
Abstract:
Cerebral malaria (CM) is one of the most serious complications of Plasmodium falciparum infection. It is characterized by sequestration of parasitized red blood cells (PRBC) in cerebral capillaries and venules. Although the exact cause of CM remains unclear, current evidence has clearly implicated metabolic disturbances and host immune responses. Studies on mouse CM models suggest the involvement of host cells and in particular platelets. These results led us to study the role of platelets in human CM. Our findings demonstrated that significantly greater accumulation of platelets occurred in capillaries and venules of Malawian patients who died from CM than from other diseases. We also assessed the role of platelets in cytoadherence of PRBCs using PRBC adhering only on CD36, platelets and endothelial cells (EC) constitutively devoid of CD36. Cultures using the three components showed that platelets played a role in inducing cytoadherence of PRBC on EC via a cellular bridging resistant to physiological flow conditions. Having established the link between platelets and sequestration, the next step will be to examine the link between platelets and CM. A combination of approaches from different disciplines will be needed to gain further insight into the mechanisms underlying the complications of malaria.
Insights
Platelets accumulate in the brain during cerebral malaria (CM), a severe complication of Plasmodium falciparum infection. These platelets promote the adhesion of infected red blood cells to blood vessel walls, contributing to CM pathogenesis.
Area of Science:
- Tropical medicine
- Hematology
- Immunology
Context:
- Cerebral malaria (CM) is a severe Plasmodium falciparum complication characterized by infected red blood cell sequestration in cerebral vessels.
- While metabolic and immune factors are implicated, the precise mechanisms of CM remain elusive.
- Previous studies in mouse models suggested a role for host cells, particularly platelets.
Purpose:
- To investigate the role of platelets in human cerebral malaria.
- To determine if platelets contribute to the cytoadherence of parasitized red blood cells (PRBCs) in CM.
Summary:
- Significantly higher platelet accumulation was observed in the cerebral capillaries and venules of Malawian patients who died from CM compared to those who died from other diseases.
- Experiments demonstrated that platelets facilitate the adherence of PRBCs to endothelial cells (EC), even in the absence of CD36.
- This platelet-mediated cytoadherence was shown to be resistant to physiological flow conditions, suggesting a crucial role in parasite sequestration.
Impact:
- Establishes a link between platelet accumulation and parasite sequestration in cerebral malaria.
- Highlights platelets as a key factor in the pathogenesis of CM.
- Suggests potential therapeutic targets for preventing or treating CM by modulating platelet function or interaction with PRBCs.