Figure 2.

Simplified representation of the NOD1, NOD2, and NLRP3 signaling pathways. (A) Recognition of their specific PGN fragments agonists through their LRR domains activates the NOD1 and NOD2 receptors. Their activation facilitates the recruitment of RIPK2 that subsequently interacts with TAK1 or NEMO triggering the NF-κB or MAPK pathways. The NF-κB and MAPK pathways, stimulate the transcriptional upregulation of different types of immunomodulatory mediators such as antimicrobial peptides, proinflammatory cytokines and chemokines. (B) NLRP3 activation requires two signals. The priming (left) is provided by MAMPs, DAMPs, or pro-inflammatory cytokines leading to the transcriptional upregulation of NLRP3, other inflammasome components, pro-IL1β and pro-IL18 through NF-κB signaling. The activation signal (right) is provided by any of the numerous MAMPs or DAMPs capable of NLRP3 activation such as ATP, particulates, and crystals causing the NLRP3 inflammasome complex assembly and subsequent cleavage of pro-IL1β and pro-IL18 into their mature forms by active caspase-1.