Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
Nat Microbiol. 2020 Jan;5(1):14-26. doi: 10.1038/s41564-019-0623-2. Epub 2019 Dec 19.
Microbial pathogens possess an arsenal of strategies to invade their hosts, evade immune defences and promote infection. In particular, bacteria use virulence factors, such as secreted toxins and effector proteins, to manipulate host cellular processes and establish a replicative niche. Survival of eukaryotic organisms in the face of such challenge requires host mechanisms to detect and counteract these pathogen-specific virulence strategies. In this Review, we focus on effector-triggered immunity (ETI) in metazoan organisms as a mechanism for pathogen sensing and distinguishing pathogenic from non-pathogenic microorganisms. For the purposes of this Review, we adopt the concept of ETI formulated originally in the context of plant pathogens and their hosts, wherein specific host proteins 'guard' central cellular processes and trigger inflammatory responses following pathogen-driven disruption of these processes. While molecular mechanisms of ETI are well-described in plants, our understanding of functionally analogous mechanisms in metazoans is still emerging. In this Review, we present an overview of ETI in metazoans and discuss recently described cellular processes that are guarded by the host. Although all pathogens manipulate host pathways, we focus primarily on bacterial pathogens and highlight pathways of effector-triggered immune defence that sense disruption of core cellular processes by pathogens. Finally, we discuss recent developments in our understanding of how pathogens can evade ETI to overcome these host adaptations.
微生物病原体拥有一系列策略来入侵宿主、逃避免疫防御并促进感染。特别是，细菌利用毒力因子，如分泌的毒素和效应蛋白，来操纵宿主细胞过程并建立复制生态位。真核生物在面对这种挑战时的生存需要宿主机制来检测和对抗这些特定于病原体的毒力策略。在这篇综述中，我们专注于后生动物生物体中的效应触发免疫 (ETI)，将其作为一种用于病原体检测和区分致病性和非致病性微生物的机制。为了本综述的目的，我们采用了最初在植物病原体及其宿主背景下提出的 ETI 概念，其中特定的宿主蛋白“保护”核心细胞过程，并在这些过程被病原体驱动破坏后引发炎症反应。虽然 ETI 的分子机制在植物中已有很好的描述，但我们对后生动物中功能类似机制的理解仍在不断发展。在这篇综述中，我们概述了后生动物中的 ETI，并讨论了最近描述的宿主保护的细胞过程。尽管所有病原体都操纵宿主途径，但我们主要关注细菌病原体，并强调了感知病原体破坏核心细胞过程的效应触发免疫防御途径。最后，我们讨论了我们对病原体如何逃避 ETI 以克服这些宿主适应的理解的最新进展。
