Lipid Trafficking and Disease Group, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Josep Carreras Leukemia Research Institute, Barcelona, Spain.
Immunol Rev. 2023 Aug;317(1):113-136. doi: 10.1111/imr.13199. Epub 2023 Mar 24.
Microbes have developed many strategies to subvert host organisms, which, in turn, evolved several innate immune responses. As major lipid storage organelles of eukaryotes, lipid droplets (LDs) are an attractive source of nutrients for invaders. Intracellular viruses, bacteria, and protozoan parasites induce and physically interact with LDs, and the current view is that they "hijack" LDs to draw on substrates for host colonization. This dogma has been challenged by the recent demonstration that LDs are endowed with a protein-mediated antibiotic activity, which is upregulated in response to danger signals and sepsis. Dependence on host nutrients could be a generic "Achilles' heel" of intracellular pathogens and LDs a suitable chokepoint harnessed by innate immunity to organize a front-line defense. Here, we will provide a brief overview of the state of the conflict and discuss potential mechanisms driving the formation of the 'defensive-LDs' functioning as hubs of innate immunity.
微生物已经开发出许多策略来颠覆宿主生物体,而宿主生物体则进化出几种先天免疫反应。作为真核生物的主要脂质储存细胞器,脂滴(LDs)是入侵物的有吸引力的营养来源。细胞内病毒、细菌和原生动物寄生虫诱导并与 LDs 发生物理相互作用,目前的观点是它们“劫持”LDs 以利用宿主定植的底物。这一教条受到了最近的一项证明的挑战,即 LDs 具有蛋白质介导的抗生素活性,这种活性会被危险信号和败血症上调。对宿主营养物质的依赖可能是细胞内病原体的一个通用的“致命弱点”,而 LDs 则是先天免疫用来组织一线防御的一个合适的阻塞点。在这里,我们将简要概述冲突的现状,并讨论驱动“防御性 LD”形成的潜在机制,这些 LD 充当先天免疫的枢纽。