小柯机器人

脂滴可作为天然免疫的枢纽
2020-10-16 15:36

西班牙巴塞罗那大学Albert Pol等研究人员合作发现,哺乳动物脂质滴是整合细胞代谢和宿主防御的先天免疫枢纽。2020年10月16日,《科学》发表了这一成果。

在所有的真核细胞中,脂滴(LD)都负责存储并提供必需的脂质,从而产生信号分子、膜结构单元和代谢能源。LD单层膜还可以容纳与脂质没有明显关系的蛋白质,例如转录因子、染色质组分和有毒蛋白质。常见的寄生虫(例如锥虫和恶性疟原虫)、细菌(例如分枝杆菌和衣原体)以及病毒(例如丙型肝炎和登革热)会在生命周期中诱导并靶向LD。目前的观点是,LD促进感染,并为微生物提供生长的底物。
 
研究人员首次证明,哺乳动物的LD具有蛋白质介导的抗菌能力,该能力被危险信号上调。在响应脂多糖(LPS)时,多种宿主防御蛋白会在LD上组装成复杂的簇,包括干扰素诱导的鸟苷三磷酸酶和抗菌肽cathelicidin。LPS还能促进LD与线粒体的物理和功能解偶联,减少脂肪酸代谢,同时增加LD与细菌的接触。因此,LD在两个水平上积极参与哺乳动物的先天免疫:它们都是组织和使用免疫蛋白杀死细胞内病原体的细胞自主细胞器,也是对抗感染时局部和全身性新陈代谢适应的核心参与者。
 
附:英文原文

Title: Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense

Author: Marta Bosch, Miguel Sánchez-álvarez, Alba Fajardo, Ronan Kapetanovic, Bernhard Steiner, Filipe Dutra, Luciana Moreira, Juan Antonio López, Rocío Campo, Montserrat Marí, Frederic Morales-Paytuví, Olivia Tort, Albert Gubern, Rachel M. Templin, James E. B. Curson, Nick Martel, Cristina Català, Francisco Lozano, Francesc Tebar, Carlos Enrich, Jesús Vázquez, Miguel A. Del Pozo, Matthew J. Sweet, Patricia T. Bozza, Steven P. Gross, Robert G. Parton, Albert Pol

Issue&Volume: 2020/10/16

Abstract: Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts. Thus, LDs actively participate in mammalian innate immunity at two levels: They are both cell-autonomous organelles that organize and use immune proteins to kill intracellular pathogens as well as central players in the local and systemic metabolic adaptation to infection.

DOI: 10.1126/science.aay8085

Source: https://science.sciencemag.org/content/370/6514/eaay8085

Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037
官方网址:https://www.sciencemag.org/
投稿链接:https://cts.sciencemag.org/scc/#/login

本期文章:《科学》:Volume 370 Issue 6514

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