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结核分枝杆菌感染人巨噬细胞后宿主反应的定量蛋白质组学分析。

Quantitative proteomic analysis of host responses triggered by Mycobacterium tuberculosis infection in human macrophage cells.

机构信息

State Key Laboratory of Agromicrobiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, and Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2017 Sep 1;49(9):835-844. doi: 10.1093/abbs/gmx080.

Abstract

Macrophages are primary host of Mycobacterium tuberculosis (M.tb) and the central effector of in vivo innate immune responses against bacteria. Though the interaction between macrophages and mycobacteria has been widely investigated, the molecular mechanisms of M.tb pathogenesis in macrophages are still not clear. In this work, we investigated the altered protein expression profiles of macrophages after virulent H37Rv strain and avirulent H37Ra strain infection by tandem mass tag-based quantitative proteomics. Among 6762 identified proteins of macrophages, the expression levels of 235 proteins were significantly altered, which is supposed to be related to the infection of different strains. By bioinformatics analysis at systems level, we found that these proteins are mainly involved in the biological process of apoptosis, blood coagulation, oxidative phosphorylation, and others. The enormous variation in protein profiles between macrophages infected with H37Ra and H37Rv suggests the existence of four different immunity mechanisms that decide the fates of macrophages and M.tb. These data may provide a better understanding of M.tb pathogenesis within the host, which contributes to the prevention and clinical treatment of tuberculosis.

摘要

巨噬细胞是结核分枝杆菌(M.tb)的主要宿主,也是体内针对细菌固有免疫反应的核心效应细胞。尽管巨噬细胞与分枝杆菌的相互作用已被广泛研究,但巨噬细胞中 M.tb 发病机制的分子机制仍不清楚。在这项工作中,我们通过串联质量标签定量蛋白质组学研究了毒力 H37Rv 株和无毒 H37Ra 株感染后巨噬细胞的蛋白质表达谱变化。在鉴定的 6762 种巨噬细胞蛋白中,有 235 种蛋白的表达水平发生了显著变化,这可能与不同菌株的感染有关。通过系统水平的生物信息学分析,我们发现这些蛋白主要参与凋亡、血液凝固、氧化磷酸化等生物学过程。H37Ra 和 H37Rv 感染的巨噬细胞之间蛋白质谱的巨大差异表明存在四种不同的免疫机制,决定了巨噬细胞和 M.tb 的命运。这些数据可能有助于更好地理解宿主内的 M.tb 发病机制,从而有助于预防和临床治疗结核病。

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