NOD-like and Toll-like receptors or inflammasomes contribute to kidney disease in a canonical and a non-canonical manner  Hans-Joachim Anders, Maciej Lech  Kidney International  Volume 84, Issue 2, Pages 225-228 (August 2013) DOI: 10.1038/ki.2013.122 Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 1 Biological effects of innate pattern recognition receptors in AKI and CKD. Left: Canonical danger signaling pathways. Toll-like receptors (TLRs), NOD-like receptors (NLRs), and NLRP inflammasomes are germ line–encoded pattern recognition receptors that translate danger recognition into the activation of proinflammatory signaling pathways and transcription factors, such as nuclear factor-κB (NF-κB). This induces the secretion of multiple proinflammatory cytokines and chemokines, which sets up inflammation for danger control, usually involving some immunopathology, especially in acute kidney injury (AKI). Right: Pyroptosis and non-canonical danger signaling pathways. In chronic kidney injury, additional non-canonical functions of these receptor classes may affect outcomes, such as TLR-mediated shifts in the activation of macrophage phenotypes, NOD-mediated alterations of glucose handling and slit-membrane proteins in podocytes, and NLRP3-mediated pyroptosis or effects on transforming growth factor-β (TGF-β) signaling. AP1, activator protein 1; ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; Co-Smads, common mediator Smads; ECM, extracellular matrix; EMT, epithelial–mesenchymal transition; GLUT4, glucose transporter-4; IKK, IκB kinase complexes; IL, interleukin; IRAK, interleukin-1-receptor-associated kinase; IRF, interferon regulatory factor; I-Smads, inhibitory Smads; ISRE, interferon-stimulated response element; MKK, mitogen-activated protein kinase kinase; MyD88, myeloid differentiation primary response gene 88; NAP1, nucleosome assembly protein 1; NOD, nucleotide-binding oligomerization domain; R-Smads, receptor-regulated Smads; TAK1, transforming growth factor beta-activated kinase 1; TGFR, transforming growth factor receptor; TRAF, tumor necrosis factor receptor–associated factor; TRIF, TIR-domain-containing adaptor-inducing interferon-β. Kidney International 2013 84, 225-228DOI: (10.1038/ki.2013.122) Copyright © 2013 International Society of Nephrology Terms and Conditions