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宿主对细胞内病原体的炎症反应:综述研究。

Host inflammatory responses to intracellular invaders: Review study.

机构信息

International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.

出版信息

Life Sci. 2020 Jan 1;240:117084. doi: 10.1016/j.lfs.2019.117084. Epub 2019 Nov 21.

DOI:10.1016/j.lfs.2019.117084
PMID:31759040
Abstract

As soon as a pathogen invades through the physical barriers of its corresponding host, host mounts a series of protective immune response to get rid of the invading pathogen. Host's pattern recognition receptors (PRR), localized at the cellular surface, cytoplasm and also in the nucleus; recognises pathogen associated molecular patterns (PAMPs) and plays crucial role in directing the immune response to be specific. Inflammatory responses are among the earliest strategies to tackle the pathogen by the host and are tightly regulated by multiple molecular pathways. Inflammasomes are multi-subunit protein complex consisting of a receptor molecule viz. NLRP3, an adaptor molecule- Apoptosis-associated speck-like protein containing a CARD (ASC) and an executioner caspase. Upon infection and/or injury; inflammasome components assemble and oligomerizes leading to the auto cleavage of the pro-caspase-1 to its active form. The activated caspase-1 cleaves immature form of the pro-inflammatory cytokines to their mature form e.g. IL1-β and IL-18 which mount inflammatory response. Moreover, C-terminal end of the Gasdermin D molecule is also cleaved by the caspase-1. The activated N-terminal Gasdermin D molecule form pores in the infected cells leading to their pyroptosis. Hence, inflammasomes drive inflammation during infection and controls the establishment of the pathogen by mounting inflammatory response and activation of the pyroptotic cell death.

摘要

一旦病原体通过相应宿主的物理屏障入侵,宿主就会启动一系列保护性免疫反应来清除入侵的病原体。宿主的模式识别受体(PRR)位于细胞表面、细胞质和细胞核中;识别病原体相关分子模式(PAMPs),并在指导免疫反应特异性方面发挥关键作用。炎症反应是宿主应对病原体的最早策略之一,受到多种分子途径的严格调控。炎性小体是一种多亚基蛋白复合物,由受体分子(如 NLRP3)、衔接子分子(含有 CARD 的凋亡相关斑点样蛋白,即 ASC)和执行半胱天冬酶组成。在感染和/或损伤时;炎性小体组件组装并寡聚化,导致前半胱天冬酶-1自身切割成其活性形式。活化的半胱天冬酶-1将不成熟的促炎细胞因子切割成成熟形式,例如白细胞介素-1β(IL1-β)和白细胞介素-18(IL-18),引发炎症反应。此外,Gasdermin D 分子的 C 末端也被半胱天冬酶-1切割。活化的 N 端 Gasdermin D 分子在受感染细胞中形成孔,导致细胞发生细胞焦亡。因此,炎性小体在感染过程中引发炎症,并通过引发炎症反应和激活细胞焦亡来控制病原体的建立。

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