From inflammasomes to fevers, crystals and hypertension: how basic research explains inflammatory diseases.
Pattern-recognition receptors, such as Toll-like receptors and NOD-like receptors (NLRs), are able through the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns to sense microbe-dependent and microbe-independent danger and thereby initiate innate immune responses. In some autoinflammatory conditions, abnormalities in NLR signaling pathways are involved in pathogenesis, as exemplified by NOD2 mutations associated with Crohn's disease. Some other NLRs are components of the inflammasome, a caspase-1- and prointerleukin-1beta-activating complex. Clinical and experimental studies are beginning to reveal the central role of the inflammasome in innate immunity. Here, we focus on monogenic hereditary inflammatory diseases, such as Muckle-Wells syndrome, which are associated with mutations in proteins that modulate the activity of the inflammasome, and on some multifactorial disorders, such as Type 2 diabetes and hypertension.
McDermott
Michael F
MF
Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds LS9 7TF, UK.
Tschopp
Jürg
J
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005334:Fever / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D053472:Nod Signaling Adaptor Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism