Department of Medicine, University of Cambridge, Cambridge, UK.
Signaling Programme, Babraham Institute, Cambridge, UK.
Eur J Clin Invest. 2018 Dec;48(12):e13028. doi: 10.1111/eci.13028. Epub 2018 Oct 15.
Critical illness is an aetiologically and clinically heterogeneous syndrome that is characterised by organ failure and immune dysfunction. Mortality in critically ill patients is driven by inflammation-associated organ damage and a profound vulnerability to nosocomial infection. Both factors are influenced by the activated complement protein C5a, released by unbridled activation of the complement system during critical illness. C5a exerts deleterious effects on organ systems directly and suppresses antimicrobial functions of key immune cells. Whilst several recent reports have added key knowledge of the cellular signalling pathways triggered by C5a, there remain a number of areas that are incompletely understood and therapeutic opportunities are still being evaluated. In this review, we summarise the cellular basis for C5a-induced vulnerability to nosocomial infection and organ dysfunction. We focus on cells of the innate immune system, highlighting the major areas in need of further research and potential avenues for targeted therapies.
危重病是一种病因学和临床异质性综合征，其特征为器官衰竭和免疫功能障碍。重症患者的死亡率由炎症相关的器官损伤和对医院感染的严重易感性驱动。这两个因素都受到补体蛋白 C5a 的影响，它是在危重病期间补体系统不受控制的激活释放的。C5a 直接对器官系统产生有害影响，并抑制关键免疫细胞的抗菌功能。虽然最近有几项报告增加了对 C5a 触发的细胞信号通路的关键知识，但仍有一些领域尚未完全理解，治疗机会仍在评估中。在这篇综述中，我们总结了 C5a 诱导医院感染和器官功能障碍易感性的细胞基础。我们专注于先天免疫系统的细胞，强调需要进一步研究的主要领域和潜在的靶向治疗途径。
