新出现的炎症小体复合物及其在炎症和脓毒症中的激活和信号传导的分子机制。

IF 7.5 2区 医学 Q1 IMMUNOLOGY
Abhimanu Pandey, Zheyi Li, Manjul Gautam, Aritra Ghosh, Si Ming Man
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引用次数: 0

摘要

炎症小体是一种多蛋白复合物,当哺乳动物细胞对病原体相关分子模式(PAMP)或损伤相关分子模式(DAMP)做出反应时,炎症小体就会在细胞质内集结,驱动促炎细胞因子IL-1β和IL-18的分泌,并导致细胞脓毒症。特征最明显的炎症小体复合物是 NLRP3、NAIP-NLRC4、NLRP1、AIM2 和 Pyrin 正常的含 caspase-1 的炎症小体,以及 caspase-11 非正常的炎症小体。新的炎性体传感器蛋白已被发现,包括 NLRP6、NLRP7、NLRP9、NLRP10、NLRP11、NLRP12、CARD8 和 MxA。这些炎性体传感器可以感知来自细菌、病毒和原生动物的 PAMPs 或线粒体损伤、ROS、压力和血红素形式的 DAMPs。人们开始认识到这些新型炎性体的作用机制、生理相关性、对人类疾病的影响以及治疗干预的途径。在此,我们将讨论这些新兴的炎症小体复合物及其假定的激活机制、分子和信号传导途径,以及在健康和疾病中的生理作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.

Inflammasomes are multi-protein complexes that assemble within the cytoplasm of mammalian cells in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), driving the secretion of the pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis. The best-characterized inflammasome complexes are the NLRP3, NAIP-NLRC4, NLRP1, AIM2, and Pyrin canonical caspase-1-containing inflammasomes, and the caspase-11 non-canonical inflammasome. Newer inflammasome sensor proteins have been identified, including NLRP6, NLRP7, NLRP9, NLRP10, NLRP11, NLRP12, CARD8, and MxA. These inflammasome sensors can sense PAMPs from bacteria, viruses and protozoa, or DAMPs in the form of mitochondrial damage, ROS, stress and heme. The mechanisms of action, physiological relevance, consequences in human diseases, and avenues for therapeutic intervention for these novel inflammasomes are beginning to be realized. Here, we discuss these emerging inflammasome complexes and their putative activation mechanisms, molecular and signaling pathways, and physiological roles in health and disease.

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来源期刊
Immunological Reviews
Immunological Reviews 医学-免疫学
CiteScore
16.20
自引率
1.10%
发文量
118
审稿时长
4-8 weeks
期刊介绍: Immunological Reviews is a specialized journal that focuses on various aspects of immunological research. It encompasses a wide range of topics, such as clinical immunology, experimental immunology, and investigations related to allergy and the immune system. The journal follows a unique approach where each volume is dedicated solely to a specific area of immunological research. However, collectively, these volumes aim to offer an extensive and up-to-date overview of the latest advancements in basic immunology and their practical implications in clinical settings.
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