Purinergic mechanism in the immune system: A signal of danger for dendritic cells

Abstract

There is increasing appreciation that injured or stressed cells release molecules endowed with the ability to modulate dendritic cell maturation. The role of these molecules is thought to be that of alerting the body of an impending danger, and initiate and shape the subsequent immune response. Nucleotides are perfectly suited for this task as they are easily released upon damage of the cell membrane, rapidly diffuse in the extracellular environment and ligate specific plasma membrane receptors expressed by dendritic cells and other mononuclear phagocytes. A better knowledge of the modulation of dendritic cell responses by extracellular nucleotides may provide novel routes to enhance the immune response and increase the efficacy of vaccination.

Figure 1

Cell damage caused by physical trauma or pathogens causes an initial wave of ATP release (red) from injured cells. This first wave of ATP release diffuses through the pericellular space and activates adjacent cells (e.g. epithelial cells, macrophages, fibroblasts). P2 receptors expressed on the plasma membrane of the bystander cells will be activated and trigger the release of several bioactive agents, among which ATP itself (ATP-induced ATP release, dark blue). Accumulation of ATP into the extracellular milieu will prime Langerhans/dendritic cells (DC) and modify their responses to bacterial endotoxin (LPS) or T lymphocyte-derived CD40 ligand (CD40L). The combined action of these agents drives DC maturation and the secretion of cytokines and chemokines.