The role of platelets in the protection against malarial infection
We have discovered that platelets in the circulation directly target and kill the malarial parasite as it grows inside red blood cells. This was a completely novel finding at the time as platelets are traditionally thought of as merely mediators of haemostasis and clot formation. However a large body of evidence now indicates their importance in many immunological and host defence functions, including malaria protection. Platelets preferentially bind to Plasmodium-infected cells, become activated and release a molecule called Platelet factor 4 (PF4), which is cytotoxic to the parasite. The PF4 molecule enters the cell and parasite via red cell molecule called Duffy. Parasites growing in red cells that lack Duffy are killed by the platelet. These discoveries implicate a relationship between the Duffy-negative allele and rates of P. falciparum infection; both are highly prevalent in African populations. Our current work aims to address a number of important questions relating to these findings, including the molecular mechanisms involved in the platelet killing function, the reasons for platelet loss early in malarial infection, and the occurrence of platelet-mediated parasite killing amongst different human populations.
- McMorran, BJ, Marshall, VM, de Graaf, C, et al., 2009, Platelets kill intraerythrocytic malarial parasites and mediate survival to infection. Science 323:797-800.
- McMorran, BJ, Wieczorski, L, Drysdale, KE, et al., 2012, Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum. Science 338:1348-1351.
- McMorran, BJ, Burgio, G, Foote, SJ., 2013, New Insights Into The Protective Power Of Platelets In Malaria Infection. Communicative & Integrative Biology 1;6(3):e23653.
- McMorran, Foote and Burgio. The role of Duffy and PF4 in platelet killing of malaria parasites. NHMRC Project Grant APP1066502