Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA; Department of Biosciences, University of Salzburg, A-5020, Salzburg, Austria.
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA.
Mol Aspects Med. 2020 Dec;76:100863. doi: 10.1016/j.mam.2020.100863. Epub 2020 Jun 1.
In this review we give an overview of the NAIP/NLRC4 activation mechanism as well as the described roles of this inflammasome, with a focus on in vivo infection and pathology. After ligand recognition by NAIP sensor proteins the NAIP/NLRC4 inflammasome forms through oligomerization with the NLRC4 adaptor to activate Caspase-1. The activating ligands are intracellular bacterial flagellin or type-3 secretion system components, delivered by pathogens. In vivo experiments indicate a role in macrophages during lung, spleen and liver infection and systemic sepsis like conditions, as well as in intestinal epithelial cells. Upon NAIP/NLRC4 activation in the intestine, epithelial cell extrusion is triggered in addition to the canonical inflammasome outcomes of cytokine cleavage and pyroptosis. Human patients with auto-activating mutations in NLRC4 present with an autoinflammatory syndrome including enterocolitis. Although one of the better understood inflammasomes in terms of mechanism, tissue specific functions of NAIP/NLRC4 are only beginning to be understood.
在这篇综述中，我们概述了 NAIP/NLRC4 激活机制以及该炎症小体的描述作用，重点介绍了体内感染和病理学。在 NAIP 传感器蛋白识别配体后，NAIP/NLRC4 炎症小体通过与 NLRC4 衔接蛋白的寡聚化形成，从而激活 Caspase-1。激活配体是细胞内细菌鞭毛蛋白或 III 型分泌系统成分，由病原体递送至细胞内。体内实验表明，它在肺、脾和肝感染以及全身性败血症等条件下的巨噬细胞中发挥作用，也在肠道上皮细胞中发挥作用。在肠道中 NAIP/NLRC4 被激活后，除了细胞因子切割和细胞焦亡的经典炎症小体结果外，还会触发上皮细胞挤出。具有 NLRC4 自动激活突变的人类患者表现出自炎症综合征，包括肠炎。尽管 NLRC4 在机制方面是理解得较好的炎症小体之一，但 NAIP/NLRC4 的组织特异性功能才刚刚开始被理解。
