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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 464-476 |
| Number of pages | 13 |
| Journal | Immunity |
| Volume | 36 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 23 2012 |
Funding
This work was supported by the National Institutes of Health (GM071723, GM071723-S1, AI082406, AI082406-S1/S2, and AR057216 to C.S.). S.K. is an Arthritis Foundation fellow (AF161715) and L.deA. is supported by the American Heart Association (11POST585000). This work was supported by the Northwestern University Monoclonal Antibody Facility, Flow Cytometry Facility, a Cancer Center Support Grant (CA060553), and the Skin Disease Research Center (P30AR057216). We thank S. Kramer for isolation of PBMCs and C. Cuda and H. Perlman for help with flow cytometry.
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
