| Abstract: | Microbialpathogens subvert host adhesion molecules to disseminate or to enterhost cells to promote their own survival. One such subversion is thecytoadherence of Plasmodiumfalciparum-infected erythrocytes (IRBC) to vascularendothelium, which protects the parasite from being removed by thespleen. The process results in microcirculatory obstruction andsubsequent hypoxia, metabolic disturbances, and multiorgan failure,which are detrimental to the host. Understanding the molecular eventsinvolved in these adhesive interactions is therefore critical both interms of pathogenesis and implications for therapeutic intervention.Under physiological flow conditions, cytoadherence occurs in a stepwisefashion through parasite ligands expressed on the surface of IRBCand the endothelial receptors CD36, intercellular adhesionmolecule-1 (ICAM-1), P-selectin, and vascular adhesion molecule-1.Moreover, rolling on ICAM-1 and P-selectin increases subsequentadhesion to CD36, indicating that receptors can act synergistically.Cytoadherence may activate intracellular signaling pathways in bothendothelial cells and IRBC, leading to gene expression of mediatorssuch as cytokines, which could modify the outcome of the infection. |
