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炎性小体与细菌病原体之间的复杂相互作用:作用、机制及治疗潜力

The intricate interactions between inflammasomes and bacterial pathogens: Roles, mechanisms, and therapeutic potentials.

作者信息

Kim Jin Kyung, Sapkota Asmita, Roh Taylor, Jo Eun-Kyeong

机构信息

Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.

Department of Microbiology, Chungnam National University College of Medicine, Daejeon, Republic of Korea; Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

出版信息

Pharmacol Ther. 2025 Jan;265:108756. doi: 10.1016/j.pharmthera.2024.108756. Epub 2024 Nov 23.

Abstract

Inflammasomes are intracellular multiprotein complexes that consist of a sensor, an adaptor, and a caspase enzyme to cleave interleukin (IL)-1β and IL-18 into their mature forms. In addition, caspase-1 and -11 activation results in the cleavage of gasdermin D to form pores, thereby inducing pyroptosis. Activation of the inflammasome and pyroptosis promotes host defense against pathogens, whereas dysregulation of the inflammasome can result in various pathologies. Inflammasomes exhibit versatile microbial signal detection, directly or indirectly, through cellular processes, such as ion fluctuations, reactive oxygen species generation, and the disruption of intracellular organelle function; however, bacteria have adaptive strategies to manipulate the inflammasome by altering microbe-associated molecular patterns, intercepting innate pathways with secreted effectors, and attenuating inflammatory and cell death responses. In this review, we summarize recent advances in the diverse roles of the inflammasome during bacterial infections and discuss how bacteria exploit inflammasome pathways to establish infections or persistence. In addition, we highlight the therapeutic potential of harnessing bacterial immune subversion strategies against acute and chronic bacterial infections. A more comprehensive understanding of the significance of inflammasomes in immunity and their intricate roles in the battle between bacterial pathogens and hosts will lead to the development of innovative strategies to address emerging threats posed by the expansion of drug-resistant bacterial infections.

摘要

炎性小体是细胞内的多蛋白复合物,由一个传感器、一个接头蛋白和一种半胱天冬酶组成,可将白细胞介素(IL)-1β和IL-18切割成成熟形式。此外,半胱天冬酶-1和-11的激活会导致gasdermin D的切割以形成孔道,从而诱导细胞焦亡。炎性小体的激活和细胞焦亡促进宿主对病原体的防御,而炎性小体的失调可导致各种病理状况。炎性小体通过细胞过程,如离子波动、活性氧生成和细胞内细胞器功能的破坏,直接或间接地表现出多种微生物信号检测功能;然而,细菌具有适应性策略,可通过改变微生物相关分子模式、用分泌的效应物拦截固有途径以及减弱炎症和细胞死亡反应来操纵炎性小体。在本综述中,我们总结了炎性小体在细菌感染期间的多种作用的最新进展,并讨论了细菌如何利用炎性小体途径来建立感染或持续存在。此外,我们强调了利用细菌免疫颠覆策略对抗急性和慢性细菌感染的治疗潜力。对炎性小体在免疫中的重要性及其在细菌病原体与宿主之间的斗争中的复杂作用有更全面的了解,将有助于开发创新策略,以应对耐药细菌感染扩大带来的新威胁。

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