Bacteria and endothelial cells: a toxic relationship

Abstract

Pathogenic bacteria use the bloodstream as a highway for getting around the body, and thus have to find ways to enter and exit through the endothelium. Many bacteria approach this problem by producing toxins that can breach the endothelial barrier through diverse creative mechanisms, including directly killing endothelial cells (ECs), weakening the cytoskeleton within ECs, and breaking the junctions between ECs. Toxins can also modulate the immune response by influencing endothelial biology, and can modulate endothelial function by influencing the response of leukocytes. Understanding these interactions, in both the in vitro and in vivo contexts, is of critical importance for designing new therapies for sepsis and other severe bacterial diseases.

Figure 1

The many ways bacteria can interact with ECs. Bacteria can adhere to ECs, and use type 3 or 4 secretion systems to inject toxins. Bacteria can secrete toxins into the bloodstream which then bind to ECs (in some cases through a receptor) and kill the cells. OMVs can also be used to deliver toxins to ECs. Toxins can also manipulate cells to disrupt their cytoskeleton and their contacts with other ECs. Toxins and OMVs can modulate the inflammatory state of ECs, affecting leukocyte adhesion molecules and cytokines, to increase or decrease leukocyte migration to the area. The end results of these actions can include bacterial breach of the endothelium, leakage of plasma and edema, and increased or decreased leukocyte migration and leukocyte-mediated damage in infected tissues.