Fig. 3. NLR- and TLR-mediated regulation of cytokine production and autophagosome formation.

Members of the Toll-like receptor (TLR) and NOD-like receptor (NLR) families recognize conserved microbial components called pathogen-associated molecular patterns (PAMPs) that correspond with molecules vital for microbial survival such as flagellin, nucleic acid structures unique to bacteria and viruses and bacterial cell wall components such as lipopolysaccharide (LPS). TLRs are located at the cell surface and in endosomes of immune cells, whereas NOD-like receptors (NLRs) and HIN-200 proteins detect pathogens located in intracellular compartments. PAMP recognition by these receptors triggers a number of protective responses, including the production of pro-inflammatory cytokines and chemokines through activation of the transcription factors NF-κB and AP-1. In addition, the NLR proteins Nod1 and Nod2 may regulate antigen presentation and bacterial clearance by promoting autophagosome formation through the recruitment of Atg16L1 to the plasma membrane. Finally, the NLRs Nlrp1b, Nlrp3 and Nlrc4; and the HIN-200 protein AIM2 induce assembly of inflammasome complexes, which are responsible for caspase-1 activation and the subsequent secretion of mature IL-1β and IL-18.