An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages.
An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages.
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DOI：
10.1016/j.immuni.2012.02.001
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发表时间：
2012-03-23
期刊：
影响因子：
32.4
通讯作者：
Stehlik C
中科院分区：
文献类型：
--
作者：
Khare S;Dorfleutner A;Bryan NB;Yun C;Radian AD;de Almeida L;Rojanasakul Y;Stehlik C
细胞内病原体和损伤相关的分子模式是由模式识别受体感知的，包括核苷酸结合域和富含亮氨酸重复序列的基因家族成员，它们引起炎症体组装和半胱氨酸蛋白酶-1激活，促进炎性细胞因子白介素1β和白介素18的成熟和释放，并诱导上睑下垂。然而，大多数NLR对天然免疫、宿主防御、炎性小体激活及其特异性激动剂的作用仍不清楚。在这里，我们描述了人巨噬细胞中NLRP7炎症体的鉴定和特征，该炎症体是由微生物酰化脂肽诱导的。NLRP7的激活促进了Caspase-1激活，IL-1β和IL-18成熟，抑制了细胞内细菌复制，但不能促进非依赖于Caspase-1的促炎细胞因子IL-6和肿瘤坏死因子-α的分泌。因此，我们的研究增加了我们目前对NLR激活、炎症体组装以及人巨噬细胞中IL-1β和IL-18成熟的有限了解。
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 (IL)-1β and IL-18 and induction of pyroptosis. However, the contribution of most of the NLRs to innate immunity, host defense, 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 pro-inflammatory 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.
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影响因子：
2.8
作者：
Bernthal, Nicholas M.;Pribaz, Jonathan R.;Stavrakis, Alexandra I.;Billi, Fabrizio;Cho, John S.;Ramos, Romela Irene;Francis, Kevin P.;Iwakura, Yoichiro;Miller, Lloyd S.
通讯作者：
Miller, Lloyd S.
DOI：
10.4049/jimmunol.0802367
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bryan NB;Dorfleutner A;Rojanasakul Y;Stehlik C
通讯作者：
Stehlik C
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
30.8
作者：
Murdoch, S;Djuric, U;Slim, R
通讯作者：
Slim, R
影响因子：
56.9
作者：
Aliprantis, AO;Yang, RB;Zychlinsky, A
通讯作者：
Zychlinsky, A