Caspase-1 inflammasomes in infection and inflammation.
Nucleotide-binding and oligomerization domain-like receptors (NLRs) constitute a family of germline-encoded pattern-recognition receptors, which allow the host to respond rapidly to a wide variety of pathogenic microorganisms. Here, we discuss recent advances in the study of a subset of NLRs, which control the activation of caspase-1 through the assembly of large protein complexes, inflammasomes. The NALP1b inflammasome recognizes anthrax lethal toxin, and flagellin from Salmonella and Legionella induces assembly of the Ipaf inflammasome. Cryopyrin/NALP3 mediates caspase-1 activation in response to a wide variety of bacterial ligands, imidazoquinolines, dsRNA, and the endogenous danger signal uric acid. The importance of these cytosolic receptors in immune regulation is underscored by the identification of mutations in cryopyrin/NALP3, which are genetically linked to human autoinflammatory disorders.
Lamkanfi
Mohamed
M
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Kanneganti
Thirumala-Devi
TD
Franchi
Luigi
L
Núñez
Gabriel
G
D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D007877:Legionnaires' Disease / Q000235:genetics / Q000276:immunology*; D018448:Models, Immunological; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology / Q000378:metabolism; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology*
D053468:CARD Signaling Adaptor Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D020170:Caspase 1