Innate Immunity and Biomaterials at the Nexus: Friends or Foes

Figure 2

Activation of the inflammasome results in the secretion of IL-1 and IL-18. Inflammasomes are activated when sensors proteins detect stimulatory ligands. The AIM2 sensor binds double stranded DNA via the HIN200 domain. The NLRP3 sensor requires two signals for activation, instigated through TLR activation (signal 1) and followed by an indicator of homeostatic disruption (signal 2). Inflammasome formation is based on homotypic interactions of the components, whereby AIM2 and NLRP3 sensors proteins recruit ASC through their PYD, allowing ASC interactions with procaspase-1 via CARD-CARD associations. This multiprotein complex forms a spherical “wheel” structure to encourage proteolytic cleavage of procaspase-1 into caspase 1. Caspase 1 functions to cleave pro-IL-1 and pro-IL-18 into their active IL-1 and IL-18 forms, respectively.