Figure 1

Model of GrA functions in cytokine release and TLR signaling. (a) Extracellular GrA can directly release proinflammatory cytokines, dependent on its catalytic activity.^{6, 7, 8, 9, 10} (b) This cytokine release is at least partly enhanced upon granzyme intracellular delivery.^{7, 8} (c) In addition, intracellular GrA can convert pro-IL-1β into bioactive IL-1β, which is secreted.^{11, 12} Furthermore, GrA potentiates TLR2/4 agonist-induced proinflammatory cytokines independent of its catalytic activity.¹⁴ (d) It may act extracellularly, for example, via binding to (cell surface) molecules to boost TLR signaling and/or (e) GrA may be taken up to fulfill an intracellular function in stimulating TLR signaling. (GrA with scissors: catalytic activity of GrA is required; GrA with scissors crossed out: catalytic activity of GrA is not required.)