Intracellular NOD-like Receptors in Host Defense and Disease Thirumala-Devi Kanneganti, Mohamed Lamkanfi, Gabriel Núñez  Immunity  Volume 27, Issue 4, Pages 549-559 (October 2007) DOI: 10.1016/j.immuni.2007.10.002 Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 1 Model for PGN Recognition by NOD1 and NOD2 The NLR proteins NOD1 and NOD2 sense intracellular iE-DAP and MDP, respectively, leading to recruitment of the adaptor proteins RICK and CARD9. Extracellular PAMPs are recognized by TLRs, which signals through MyD88, IRAK proteins, and TRAF members. For clarity, the TLR pathway has been simplified. The subsequent activation of NF-κB and MAP kinases results in the transcriptional upregulation of proinflammatory genes. Immunity 2007 27, 549-559DOI: (10.1016/j.immuni.2007.10.002) Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 2 Ligands and Composition of the Caspase-1 Inflammasomes Recognition of PAMPs by TLRs induces synthesis of the IL-1β precursor through activation of NF-κB. Bacteria and bacterial products enter the cytosol via pore-forming toxins, type III or IV secretion systems, or ATP-mediated activation of the pannexin-1 pore. Activation of NLRs by cytosolic PAMPs results in the formation of caspase-1-activating inflammasomes independently of TLRs. The inflammasome adaptor ASC is required for recruitment of caspase-1, although its role in the Nalp1b inflammasome needs to be confirmed. Salmonella and Legionella flagellin are sensed by Ipaf, whereas mouse Nalp1b recognizes anthrax lethal toxin. Cryopyrin/Nalp3 mediates caspase-1 activation in response to a wide variety of microbial components and the endogenous danger signal uric acid. Francisella induce ASC-dependent caspase-1 activation through an NLR, the identity of which is unknown. Active caspase-1 processes the IL-1β precursor into the mature cytokine, which is secreted through an unknown mechanism. Immunity 2007 27, 549-559DOI: (10.1016/j.immuni.2007.10.002) Copyright © 2007 Elsevier Inc. Terms and Conditions