Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil.
Methods Mol Biol. 2023;2696:1-27. doi: 10.1007/978-1-0716-3350-2_1.
The innate immune response represents the first line of host defense, and it is able to detect pathogen- and damage-associated molecular patterns (PAMPs and DAMPs, respectively) through a variety of pattern recognition receptors (PRRs). Among these PRRs, certain cytosolic receptors of the NLRs family (specifically NLRP1, NLRP3, NLRC4, and NAIP) or those containing at least a pyrin domain (PYD) such as pyrin and AIM2, activate the multimeric complex known as inflammasome, and its effector enzyme caspase-1. The caspase-1 induces the proteolytic maturation of the pro-inflammatory cytokines IL-1ß and IL-18, as well as the pore-forming protein gasdermin D (GSDMD). GSDMD is responsible for the release of the two cytokines and the induction of lytic and inflammatory cell death known as pyroptosis. Each inflammasome receptor detects specific stimuli, either directly or indirectly, thereby enhancing the cell's ability to sense infections or homeostatic disturbances. In this chapter, we present the activation mechanism of the so-called "canonical" inflammasomes.
先天免疫反应代表宿主防御的第一道防线，它能够通过多种模式识别受体（PRRs）检测病原体和损伤相关的分子模式（PAMPs 和 DAMPs）。在这些 PRRs 中，某些 NLRs 家族的胞质受体（特别是 NLRP1、NLRP3、NLRC4 和 NAIP）或那些至少含有一个pyrin 结构域（PYD）的受体，如 pyrin 和 AIM2，会激活称为炎症小体的多聚体复合物，以及其效应酶 caspase-1。Caspase-1 诱导前炎症细胞因子 IL-1β 和 IL-18 的蛋白水解成熟，以及形成孔的蛋白 gasdermin D (GSDMD)。GSDMD 负责两种细胞因子的释放和称为细胞焦亡的裂解和炎症细胞死亡的诱导。每个炎症小体受体直接或间接检测特定的刺激物，从而增强细胞感知感染或体内平衡紊乱的能力。在本章中，我们介绍了所谓的“经典”炎症小体的激活机制。
