病原细菌调控丝裂原激活蛋白激酶信号介导先天免疫的机制研究进展

Innate immune mechanism mediated by MAPK signaling pathway during bacterial infection

摘要:

信号传导途径使细胞能够对复杂的外界环境刺激及时做出反应，从而针对不同病原菌感染产生生物学效应。丝裂原激活蛋白激酶(mitogen-activated protein kinase，MAPK)及其下游靶标作为将环境输入转化为大量细胞程序的最重要信号模块之一，在哺乳动物细胞中最为常见，几乎参与绝大多数细胞的生理和病理反应。MAPK响应各种环境压力刺激，包括细菌感染和炎症，以此调节宿主的免疫反应。近期研究表明，病原菌在感染期间会释放特定效应物或毒素来劫持MAPK通路，劫持方式分为两种，一种是通过降解关键蛋白影响信号传导，更主要的一种是影响宿主细胞翻译后修饰，如磷酸化、泛素化等来调节诸多细胞进程。本文讨论了MAPK在先天免疫中的调节激活过程，并研究病原细菌如何进化出复杂机制来操纵MAPK激活以增强自身感染，以及作为新型抗病原感染和肿瘤免疫治疗靶点的潜在作用。

关键词:丝裂原激活蛋白激酶;先天免疫;病原感染;药物靶点

Abstract:

Signal transduction pathways enable cells to respond to different complex external environmental stimulation in time, thus producing biological effects in response to infection by various pathogens. Mitogen-activated protein kinase (MAPK) and its downstream targets are among the most critical signaling modules that can transform environmental stress into many cellular processes. They are most common in mammalian cells and are almost involved in the physiological and pathological responses of all cells. MAPK regulates the host’s immune response to various environmental stress, including bacterial infection and inflammasomes. Recent studies have shown that pathogens may release specific effectors or toxins to hijack the MAPK signaling pathway during infection in two ways. One is to degrade essential proteins to affect signal transduction, and the other is to influence host cell post-translational modifications, such as phosphorylation and ubiquitination, to regulate many cellular processes. This review discussed the regulation and activation of MAPK in innate immunity and explored the complex mechanism of pathogens in manipulating MAPK activation to enhance infection and the potential role of MAPK regulated by pathogens as a novel target against pathogen infection.

Key words:mitogen-activated protein kinase;innate immunity;pathogen infection;drug target