Stowe Irma, Lee Bettina, Kayagaki Nobuhiko
Department of Physiological Chemistry, Genentech Inc., South San Francisco, CA, USA.
Immunol Rev. 2015 May;265(1):75-84. doi: 10.1111/imr.12292.
As a front line of defense against pathogenic microbes, our body employs a primitive, yet highly sophisticated and potent innate immune response pathway collectively referred to as the inflammasome. Innate immune cells, epithelial cells, and many other cell types are capable of detecting infection or tissue injury and mounting a coordinated molecular defense. For example, Gram-negative bacteria are specifically detected via a surveillance mechanism that involves activation of extracellular receptors such as Toll-like receptors (TLRs) followed by intracellular recognition and activation of pathways such as caspase-11 (caspase-4/5 in humans). Importantly, lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is a strong trigger of these pathways. Extracellular LPS primarily stimulates TLR4, which can serve as a priming signal for expression of inflammasome components. Intracellular LPS can then trigger caspase-11-dependent inflammasome activation in the cytoplasm. Here, we briefly review the burgeoning caspase-11-dependent non-canonical inflammasome field, focusing mainly on the innate sensing of LPS.
作为抵御病原微生物的第一道防线，我们的身体采用了一种原始但高度复杂且有效的固有免疫反应途径，统称为炎性小体。固有免疫细胞、上皮细胞和许多其他细胞类型能够检测感染或组织损伤，并发动协调一致的分子防御。例如，革兰氏阴性菌通过一种监测机制被特异性检测，该机制涉及细胞外受体（如Toll样受体（TLR））的激活，随后是细胞内识别和诸如半胱天冬酶-11（人类中的半胱天冬酶-4/5）等途径的激活。重要的是，革兰氏阴性菌外膜的主要成分脂多糖（LPS）是这些途径的强烈触发因素。细胞外LPS主要刺激TLR4，其可作为炎性小体成分表达的启动信号。然后，细胞内LPS可在细胞质中触发半胱天冬酶-11依赖性炎性小体激活。在此，我们简要回顾一下新兴的半胱天冬酶-11依赖性非经典炎性小体领域，主要关注LPS的固有感知。
