Molecular mechanisms of cytoadherence in malaria

Microbial pathogens subvert host adhesion molecules to disseminate or to en ter host cells to promote their own survival. One such subversion is the cy toadherence of Plasmodium falciparum-infected erythrocytes (IRBC) to vascul ar endothelium, which protects the parasite from being removed by the splee n. The process results in microcirculatory obstruction and subsequent hypox ia, metabolic disturbances, and multiorgan failure, which are detrimental t o the host. Understanding the molecular events involved in these adhesive i nteractions is therefore critical both in terms of pathogenesis and implica tions for therapeutic intervention. Under physiological flow conditions, cy toadherence occurs in a stepwise fashion through parasite ligands expressed on the surface of IRBC and the endothelial receptors CD36, intercellular a dhesion molecule-1 (ICAM-1), P-selectin, and vascular adhesion molecule-1. Moreover, rolling on ICAM-1 and P-selectin increases subsequent adhesion to CD36, indicating that receptors can act synergistically. Cytoadherence may activate intracellular signaling pathways in both endothelial cells and IR BC, leading to gene expression of mediators such as cytokines, which could modify the outcome of the infection.