Cytosolic innate immune sensing is a cornerstone of innate immunity in mammalian cells and provides a surveillance system for invading pathogens and endogenous danger signals. The NAIP‐NLRC4 inflammasome responds to cytosolic flagellin, and the inner rod and needle proteins of the type 3 secretion system of bacteria. This complex induces caspase‐1‐dependent proteolytic cleavage of the proinflammatory cytokines IL‐1β and IL‐18, and the pore‐forming protein gasdermin D, leading to inflammation and pyroptosis, respectively. Localized responses triggered by the NAIP‐NLRC4 inflammasome are largely protective against bacterial pathogens, owing to several mechanisms, including the release of inflammatory mediators, liberation of concealed intracellular pathogens for killing by other immune mechanisms, activation of apoptotic caspases, caspase‐7, and caspase‐8, and expulsion of an entire infected cell from the mammalian host. In contrast, aberrant activation of the NAIP‐NLRC4 inflammasome caused by de novo gain‐of‐function mutations in the gene encoding NLRC4 can lead to macrophage activation syndrome, neonatal enterocolitis, fetal thrombotic vasculopathy, familial cold autoinflammatory syndrome, and even death. Some of these clinical manifestations could be treated by therapeutics targeting inflammasome‐associated cytokines. In addition, the NAIP‐NLRC4 inflammasome has been implicated in the pathogenesis of colorectal cancer, melanoma, glioma, and breast cancer. However, no consensus has been reached on its function in the development of any cancer types. In this review, we highlight the latest advances in the activation mechanisms and structural assembly of the NAIP‐NLRC4 inflammasome, and the functions of this inflammasome in different cell types. We also describe progress toward understanding the role of the NAIP‐NLRC4 inflammasome in infectious diseases, autoinflammatory diseases, and cancer.

中文翻译：

---

激活 NAIP-NLRC4 炎症小体的分子机制：对传染病、自身炎症和癌症的影响。

细胞溶质先天免疫传感是哺乳动物细胞先天免疫的基石，并为入侵病原体和内源性危险信号提供监视系统。NAIP-NLRC4 炎症小体对细胞质鞭毛蛋白和细菌 3 型分泌系统的内杆和针蛋白有反应。该复合物诱导促炎细胞因子 IL-1β 和 IL-18 以及成孔蛋白 gasdermin D 的 caspase-1 依赖性蛋白水解裂解，分别导致炎症和细胞焦亡。由 NAIP-NLRC4 炎症小体触发的局部反应在很大程度上对细菌病原体具有保护作用，这归因于多种机制，包括炎症介质的释放、隐藏的细胞内病原体的释放以被其他免疫机制杀死、凋亡的 caspase、caspase-7 的激活、和 caspase-8，以及从哺乳动物宿主中排出整个受感染细胞。相比之下，NAIP-NLRC4 炎症小体的异常激活是由从头开始NLRC4 编码基因的功能获得性突变可导致巨噬细胞激活综合征、新生儿小肠结肠炎、胎儿血栓性血管病、家族性感冒自身炎症综合征，甚至死亡。其中一些临床表现可以通过靶向炎性体相关细胞因子的疗法进行治疗。此外，NAIP-NLRC4 炎症小体与结直肠癌、黑色素瘤、神经胶质瘤和乳腺癌的发病机制有关。然而，尚未就其在任何癌症类型发展中的作用达成共识。在这篇综述中，我们重点介绍了 NAIP-NLRC4 炎症小体的激活机制和结构组装的最新进展，以及该炎症小体在不同细胞类型中的功能。