INSERM, C3M, Côte D'Azur University, Nice, France.
INSERM, CNRS, CIML, Turing Centre for Living Systems, Aix-Marseille University, Marseille, France.
Cell Mol Life Sci. 2021 May;78(9):4305-4333. doi: 10.1007/s00018-021-03787-w. Epub 2021 Feb 25.
Innate immunity is an evolutionary ancient defence strategy that serves to eliminate infectious agents while maintaining host health. It involves a complex network of sensors, signaling proteins and immune effectors that detect the danger, then relay and execute the immune programme. Post-translational modifications relying on conserved ubiquitin and ubiquitin-like proteins are an integral part of the system. Studies using invertebrate models of infection, such as the nematode Caenorhabditis elegans, have greatly contributed to our understanding of how ubiquitin-related processes act in immune sensing, regulate immune signaling pathways, and participate to host defence responses. This review highlights the interest of working with a genetically tractable model organism and illustrates how C. elegans has been used to identify ubiquitin-dependent immune mechanisms, discover novel ubiquitin-based resistance strategies that mediate pathogen clearance, and unravel the role of ubiquitin-related processes in tolerance, preserving host fitness during pathogen attack. Special emphasis is placed on processes that are conserved in mammals.
先天免疫是一种古老的进化防御策略,旨在消除感染因子,同时维持宿主健康。它涉及一个复杂的传感器、信号蛋白和免疫效应器网络,这些传感器、信号蛋白和免疫效应器可以检测到危险,然后传递和执行免疫程序。依赖保守泛素和泛素样蛋白的翻译后修饰是该系统的一个组成部分。使用感染的无脊椎动物模型(如线虫秀丽隐杆线虫)的研究极大地促进了我们对泛素相关过程如何在免疫感应中发挥作用、调节免疫信号通路以及参与宿主防御反应的理解。本综述强调了使用遗传上易于操作的模式生物的重要性,并说明了秀丽隐杆线虫如何被用于鉴定依赖泛素的免疫机制、发现介导病原体清除的新的基于泛素的抗性策略、以及阐明泛素相关过程在耐受中的作用,从而在病原体攻击时保持宿主的适应性。特别强调了在哺乳动物中保守的过程。