Figure 6.

Diagrammatic representation of NAD induced T cell death (NICD) and its inhibition by rSmNPP5 and live schistosomes. A Treg cell is depicted (green) with its surface P2X7 receptor (P2X7R, blue) and ADPR ribosyl transferase ART2 (teal). NAD is a substrate for ART2 which generates nicotinamide (Nam) and ADPR; transfer of ADPR to P2X7R triggers apoptosis and this process results in exposure of phosphatidylserine (PS, pink star shapes) at the T cell surface. Cell membrane permeability increases which permits propidium iodide (PI) entry and signals late-stage apoptosis. Adult male and female schistosomes (left), through the action of surface ectoenzyme SmNPP5 (pink box), cleave extracellular NAD to NMN and AMP thus removing the ART2 substrate and preventing NAD induced Treg apoptosis.