An NLRP7-Containing Inflammasome Mediates Recognition of Microbial Lipopeptides in Human Macrophages

作者：Khare Sonal; Dorfleutner Andrea; Bryan Nicole B; Yun Chawon; Radian Alexander D; de Almeida Lucia; Rojanasakul Yon; Stehlik Christian^*

来源：Immunity, 2012, 36(3): 464-476.

DOI：10.1016/j.immuni.2012.02.001

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-1 beta (IL-1 beta) 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-1 beta 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-1 beta and IL-18 in human macrophages.

• 出版日期2012-3-23
• 单位西北大学