Extracellular Vesicles and Renal Endothelial Cells: A Fatal Attraction in Hemolytic Uremic Syndrome

Abstract

This review focuses on typical hemolytic uremic syndrome (HUS), a life-threatening sequela of human infections caused, particularly in children, by Shiga toxin-producing Escherichia coli strains. Thrombotic microangiopathy of the brain and the kidney is the end point of toxin action, resulting in the hallmarks of HUS (ie, thrombocytopenia, anemia, and acute renal failure). A growing body of evidence points to the role of extracellular vesicles released in the blood of patients by toxin-challenged circulating cells (monocytes, neutrophils, and erythrocytes) and platelets, as a key factor in the pathogenesis of HUS. This review provides i) an updated description of the pathogenesis of Shiga toxin-producing E. coli infections; ii) an analysis of blood cell-derived extracellular vesicles, and of their parent cells, as triggering factors in HUS; and iii) a model explaining why Shiga toxin-containing vesicles dock preferentially to the endothelia of target organs.