Miller Figure 3 (in Weatherall et al). The variant antigen family of PfEMP1 is central to host-parasite interaction and pathogenesis.

PfEMP1 expressed on the surface of mature P. falciparum-infected RBCs is involved with clonal antigenic variation and can bind to many host receptors through its multiple adhesion domains. The different properties of PfEMP1sequestration for evading spleen-dependent killing and antigenic variation for evasion of antibody-dependent killingcontribute to the virulence and pathogenesis of P. falciparum and are essential for the survival of the parasite. Parasite sequestration in the brain and placenta contribute to the complications of cerebral malaria and placental malaria, respectively. Simultaneous binding to several receptors, binding of uninfected erythrocytes (rosetting), and clumping of infected erythrocytes through platelets are associated with malaria pathogenesis. Parasite-infected RBCs binding to dendritic cells downregulate the host immune response.

Abbreviations: HA, hyaluronic acid; TSP, thrombospondin; ELAM-1, endothelial/leukocyte adhesion molecule 1; P-sel., P-selectin; VCAM-1, vascular cell adhesion molecule 1; CR1 complement receptor 1; HS-like GAGs, heparin sulfate-like glycosaminoglycans; IgM, immunoglobulin M.