title: An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages.
abstract: Cytosolic pathogen- and damage-associated molecular patterns are sensed by pattern recognition receptors, including members of the nucleotide-binding domain and leucine-rich repeat-containing gene family (NLR), which cause inflammasome assembly and caspase-1 activation to promote maturation and release of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and induction of pyroptosis. However, the contribution of most of the NLRs to innate immunity, host defense, and inflammasome activation and their specific agonists are still unknown. Here we describe identification and characterization of an NLRP7 inflammasome in human macrophages, which is induced in response to microbial acylated lipopeptides. Activation of NLRP7 promoted ASC-dependent caspase-1 activation, IL-1β and IL-18 maturation, and restriction of intracellular bacterial replication, but not caspase-1-independent secretion of the proinflammatory cytokines IL-6 and tumor necrosis factor-α. Our study therefore increases our currently limited understanding of NLR activation, inflammasome assembly, and maturation of IL-1β and IL-18 in human macrophages.
authors.affiliation: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Khare
authors.forename: Andrea
authors.initials: A
authors.lastname: Dorfleutner
authors.forename: Nicole B
authors.initials: NB
authors.lastname: Bryan
authors.forename: Chawon
authors.initials: C
authors.lastname: Yun
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Radian
authors.forename: Lucia
authors.initials: L
authors.lastname: de Almeida
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
authors.forename: Christian
authors.initials: C
authors.lastname: Stehlik
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000276:immunology; D020170:Caspase 1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D055666:Lipopeptides / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D046912:Multiprotein Complexes / Q000276:immunology; D009174:Mycoplasma / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C508600:IL6 protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D055666:Lipopeptides; D046912:Multiprotein Complexes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C502448:NLRP7 protein, human; C402202:PYCARD protein, human; D014409:Tumor Necrosis Factor-alpha; D020170:Caspase 1