Bovis Bacillus Calmette-Guerin (BCG) infection induces exosomal miRNA release by human macrophages.
Bovis Bacillus Calmette-Guerin (BCG) infection induces exosomal miRNA release by human macrophages.
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DOI：
10.1186/s12967-017-1205-9
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发表时间：
2017-05-12
影响因子：
7.4
通讯作者：
Adcock IM
中科院分区：
文献类型：
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作者：
Alipoor SD;Mortaz E;Tabarsi P;Farnia P;Mirsaeidi M;Garssen J;Movassaghi M;Adcock IM
结核病（TB）仍然是一个重大的全球健康问题，由于目前诊断测试的特异性和敏感性的局限性，其诊断具有挑战性。外泌体是由大多数细胞类型产生的具有生物活性的30-100纳米囊泡，几乎存在于所有人体体液中。外泌体microRNAs （miRNAs）可以在细胞和组织之间传递生物信息，并可能在许多疾病中作为潜在的生物标志物。在这项初步研究中，我们评估了人单核细胞来源的巨噬细胞感染牛分枝杆菌卡介苗（BCG）后释放的外泌体的miRNA谱。从三名健康受试者的外周血中获得人类单核细胞，并使用标准方案将其驱动为单核细胞来源的巨噬细胞（MDM）表型。MDMs感染卡介苗或不感染作为对照。感染72 h后，从细胞培养基中收集外泌体，分离RNA并进行RNA测序。对原始reads进行过滤以去除接头和引物序列，并将序列与miRBase中可用的成熟人miRNA序列进行比对。microrna鉴定的E值<0.01。使用DIANA miRNA工具、miRDB和功能性KEGG通路分析进行miRNA网络分析。MDMs感染卡介苗导致几种外泌体mirna的释放。其中包括miR-1224、-1293、-425、-4467、-4732、-484、-5094、-6848-6849、-4488和-96，预计它们都针对代谢和能量产生相关的途径。本研究为bcg感染的MDMs释放特异性外泌体mirna提供了证据。这些外泌体mirna反映了感染后宿主-病原体相互作用和宿主代谢过程的颠覆。
Tuberculosis (TB) remains a significant global health concern and its diagnosis is challenging due to the limitations in the specificity and sensitivity of the current diagnostic tests. Exosomes are bioactive 30–100 nm vesicles produced by most cell types and are found in almost all human body fluids. Exosomal microRNAs (miRNAs) can transfer biological information between cells and tissues and may act as potential biomarkers in many diseases. In this pilot study, we assessed the miRNA profile of exosomes released from human monocyte-derived macrophages upon infection with Mycobacterium bovis Bacillus Calmette–Guerin (BCG). Human monocytes were obtained from the peripheral blood of three healthy subjects and driven to a monocyte-derived macrophage (MDM) phenotype using standard protocols. MDMs were infected with BCG or left uninfected as control. 72 h post-infection, exosomes were collected from the cell culture medium, RNA was isolated and RNA-seq performed. The raw reads were filtered to eliminate adaptor and primer sequences and the sequences were run against the mature human miRNA sequences available in miRBase. MicroRNAs were identified using an E value <0.01. miRNA network analysis was performed using the DIANA miRNA tool, miRDB and functional KEGG pathway analysis. Infection of MDMs with BCG leads to the release of several exosomal miRNAs. These included miR-1224, -1293, -425, -4467, -4732, -484, -5094, -6848-6849, -4488 and -96 all of which were predicted to target metabolism and energy production-related pathways. This study provides evidence for the release of specific exosomal miRNAs from BCG-infected MDMs. These exosomal miRNAs reflect host-pathogen interaction and subversion of host metabolic processes following infection.