Immunity. 2012 Mar 23;36(3):464-76. Epub 2012 Feb 21.

An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages.External

Khare, S., Dorfleutner, A., Bryan, N. B., Yun, C., Radian, A. D., de Almeida, L., Rojanasakul, Y., Stehlik, C.,
--- - Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
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-1beta (IL-1beta) 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-1beta 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-alpha. Our study therefore increases our currently limited understanding of NLR activation, inflammasome assembly, and maturation of IL-1beta and IL-18 in human macrophages.
PMID: 22361007External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
PYD ASC Link NLRP3 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 22361007
PYD ASC Link NLRP7 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 22361007
(Link: click this icon to show interactions only between the two corresponding DDs)