FIGURE 2. TLR AND NLR SIGNALING PATHWAYS.

Pathogen-associated molecular patterns (e.g. LPS, Flagellin, bacterial peptidoglycan) bind to their specific TLR and mediate downstream effects, signaling through MyD88 and subsequently inducing proinflammatory cytokines. TLR3 and sometime TLR4 can also signal through TRIF upon binding to their ligand within the endosome, inducing proinflammatory cytokines and type I interferons to protect further cells from infection. In addition TLR7, 8 and 9 can also bind their ligand in the endosome and induce type I interferons. To help regulate these signaling pathways, molecules such as IRAK-M are present to inhibit MyD88 signaling and prevent or down-regulate the level of inflammation.

NLR signaling is believed to induce an additive response to the TLR signaling pathway. Similarly to the TLR signaling pathway, bacterial pathogen-associated molecular patterns can enter the cell and activate the cytosolic NLR signaling molecules such as NOD1/2, NLRP3 and NLRC4 (IPAF). These NLR molecules require the formation of inflammasomes (multi-subunit proteins interacting) in order to mediate their effects. While these pathways promote proinflammatory cytokines mediated through NF-KB, they also induce the activation of caspase 1, which in turn cleaves pro-IL1beta and pro-IL18 into their activated forms.