Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.
Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.
Curr Opin Microbiol. 2015 Feb;23:32-41. doi: 10.1016/j.mib.2014.10.008. Epub 2014 Nov 13.
Inflammasomes - molecular platforms for caspase-1 activation - have emerged as common hubs for a number of pathways that detect and respond to bacterial pathogens. Caspase-1 activation results in the secretion of bioactive IL-1β and IL-18 and pyroptosis, and thus launches a systemic immune and inflammatory response. In this review we discuss signal transduction leading to 'canonical' and 'non-canonical' activation of caspase-1 through the involvement of upstream caspases. Recent studies have identified a growing number of regulatory networks involving guanylate binding proteins, protein kinases, ubiquitylation and necroptosis related pathways that modulate inflammasome responses and immunity to bacterial infection. By being able to respond to extracellular, vacuolar and cytosolic bacteria, their cytosolic toxins or ligands for cell surface receptors, inflammasomes have emerged as important sentinels of infection.
炎症小体——一种能够激活半胱氨酸天冬氨酸蛋白酶-1(caspase-1)的分子平台——已经成为许多检测和响应细菌病原体的途径的共同枢纽。Caspase-1 的激活导致生物活性白细胞介素 1β(IL-1β)和白细胞介素 18(IL-18)的分泌和细胞焦亡的发生,从而引发全身性免疫和炎症反应。在这篇综述中,我们讨论了通过上游半胱氨酸天冬氨酸蛋白酶(caspase)的参与导致 caspase-1 的“经典”和“非经典”激活的信号转导。最近的研究已经确定了越来越多的调节网络,包括鸟苷酸结合蛋白、蛋白激酶、泛素化和坏死相关途径,这些调节网络调节炎症小体的反应和对细菌感染的免疫。炎症小体能够对外界、液泡和细胞质中的细菌及其细胞质毒素或细胞表面受体配体做出反应,因此成为感染的重要哨兵。