Abstract
Our understanding of the basis of severe disease in malaria is incomplete. It is clear that pathology is in part related to the pro-inflammatory nature of the host response but a number of other factors are also thought to be involved, including the interaction between infected erythrocytes and endothelium. This is a complex system involving several host receptors and a major parasite-derived variant antigen (PfEMP1) expressed on the surface of the infected erythrocyte membrane. Previous studies have suggested a role for ICAM-1 in the pathology of cerebral malaria, although these have been inconclusive. In this study we have examined the cytoadherence patterns of 101 patient isolates from varying clinical syndromes to CD36 and ICAM-1, and have used variant ICAM-1 proteins to further characterise this adhesive phenotype. Our results show that increased binding to CD36 is associated with uncomplicated malaria while ICAM-1 adhesion is raised in parasites from cerebral malaria cases.
Highlights
Infections by the human malaria parasite Plasmodium falciparum can lead to a range of severe outcomes including severe anaemia, organ failure, coma and eventually death
Children with severe disease (SMA, Cerebral Malaria (CM) and severe malaria-other) had a median age of 4 years and those with uncomplicated malaria had a median age of 5 years
CM, cerebral malaria; Severe malaria anaemia (SMA), severe malarial anemia; UM, uncomplicated malaria; SM-O, severe malaria-other-severely ill children who did not meet the criteria for severe anemia, cerebral malaria. doi:10.1371/journal.pone.0014741.t002. This current study assessed the adhesion of P. falciparum infected erythrocytes under flow (ICAM-1) and static (ICAM-1 and CD36) conditions from children with different clinical syndromes of malaria
Summary
Infections by the human malaria parasite Plasmodium falciparum can lead to a range of severe outcomes including severe anaemia, organ failure, coma and eventually death. Binding to the endothelial receptor ICAM-1 has been associated with sequestration in brain vasculature [5] and showed a weak but not statistically significant association in one study with cerebral malaria (CM), while adhesion to CD36 showed no association [6]. Other adhesive phenotypes such as formation of rosettes [7,8,9] and the ability to bind receptors expressed on the placenta [10,11,12] have consistently shown strong associations with pathology. As demonstrated in the field of pregnancy associated malaria, characterizing the molecular nature of these interactions is important in understanding the pathogenesis of the more severe forms of malaria, because it would potentially provide more information in the design of new methods of prevention and treatment [10,26,27,28,29]
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