Immune role of platelets in malaria

Abstract

Plasmodium infections causing malaria threaten over 3 billion people from more than ninety countries. Despite control efforts spanning several decades, there are still more than 400,000 fatalities annually. Survival to malaria is largely determined by the host response mounted against the parasite, and the ensuing balance of inflammatory, tissue-damaging reactions and immune-mediated mechanisms directed towards controlling pathogen growth. Platelets appear to play important roles in each of these processes. On one hand, platelets have been implicated adversely in cerebral malaria, a severe disease manifestation where microvascular occlusions develop in the brain, leading to inflammatory foci and brain swelling, and causing coma and often death. Platelets adhere to the cerebral endothelium and mediate accumulation of infected erythrocytes in the brain, with the postulated outcome of increasing severity or of even mediating this disease. On the other hand, platelets can directly kill parasites in the periphery by binding to infected red cells and thereby contribute to the host’s ability to control the infection. Platelet binding to infected red cells releases an antimicrobial protein, platelet factor 4 (PF4), which accumulates inside the cell and kills the parasite by lysing the food vacuole. The Duffy antigen, a red cell-expressed receptor of PF4, is required for the PF4 accumulation and parasite killing. Further understanding of the roles of platelets in malaria, especially in clinical disease, is required. This knowledge may provide novel interventions and therapeutic tools, which are so desperately needed.