Emerging Concepts about NAIP/NLRC4 Inflammasomes.
Emerging Concepts about NAIP/NLRC4 Inflammasomes.
复制标题
DOI：
10.3389/fimmu.2014.00309
复制
发表时间：
2014
影响因子：
7.3
通讯作者：
Bortoluci KR
中科院分区：
文献类型：
--
作者：
Lage SL;Longo C;Branco LM;da Costa TB;Buzzo Cde L;Bortoluci KR
神经元凋亡抑制蛋白(NAIP)/ nod样受体（NLR）含有半胱天蛋白酶激活和募集结构域（CARD） 4 （NLRC4）炎性体复合物，当毒力细菌的蛋白到达细胞质时，它们会被激活。特异性NAIP蛋白与激动剂结合，然后与NLRC4物理结合，形成能够招募和激活前caspase-1的炎性小体复合物。NAIP5和NAIP6分别检测来自运动细菌的鞭毛成分鞭毛蛋白，而NAIP1和NAIP2分别检测来自III型细菌分泌系统的针状和棒状成分。活性caspase-1介导促炎细胞因子IL-1β和IL-18的成熟和分泌，并负责诱导焦亡，这是一种促炎的细胞死亡形式。除了这些众所周知的效应机制外，NAIP/NLRC4炎症小体的新作用也被描述，如吞噬体成熟、诱导型一氧化氮合酶的激活、自噬调节、炎症介质的分泌、抗体的产生、T细胞的激活等。这些由NAIP/NLRC4炎症小体介导的效应机制已经在感染抵抗的背景下得到了广泛的研究，它们的激动剂的潜力已被用于非感染性病理的治疗策略，如肿瘤保护。因此，本文将讨论NAIP/NLRC4炎症小体的激活及其效应机制。
Neuronal apoptosis inhibitory protein (NAIP)/NOD-like receptor (NLR) containing a caspase activating and recruitment domain (CARD) 4 (NLRC4) inflammasome complexes are activated in response to proteins from virulent bacteria that reach the cell cytosol. Specific NAIP proteins bind to the agonists and then physically associate with NLRC4 to form an inflammasome complex able to recruit and activate pro-caspase-1. NAIP5 and NAIP6 sense flagellin, component of flagella from motile bacteria, whereas NAIP1 and NAIP2 detect needle and rod components from bacterial type III secretion systems, respectively. Active caspase-1 mediates the maturation and secretion of the pro-inflammatory cytokines, IL-1β and IL-18, and is responsible for the induction of pyroptosis, a pro-inflammatory form of cell death. In addition to these well-known effector mechanisms, novel roles have been described for NAIP/NLRC4 inflammasomes, such as phagosomal maturation, activation of inducible nitric oxide synthase, regulation of autophagy, secretion of inflammatory mediators, antibody production, activation of T cells, among others. These effector mechanisms mediated by NAIP/NLRC4 inflammasomes have been extensively studied in the context of resistance of infections and the potential of their agonists has been exploited in therapeutic strategies to non-infectious pathologies, such as tumor protection. Thus, this review will discuss current knowledge about the activation of NAIP/NLRC4 inflammasomes and their effector mechanisms.