Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages

Abstract Background 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...

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Main Authors: Shamila D. Alipoor, Esmaeil Mortaz, Payam Tabarsi, Parissa Farnia, Mehdi Mirsaeidi, Johan Garssen, Masoud Movassaghi, Ian M. Adcock
Format: Article
Language:English
Published: BMC 2017-05-01
Series:Journal of Translational Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12967-017-1205-9
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author Shamila D. Alipoor
Esmaeil Mortaz
Payam Tabarsi
Parissa Farnia
Mehdi Mirsaeidi
Johan Garssen
Masoud Movassaghi
Ian M. Adcock
author_facet Shamila D. Alipoor
Esmaeil Mortaz
Payam Tabarsi
Parissa Farnia
Mehdi Mirsaeidi
Johan Garssen
Masoud Movassaghi
Ian M. Adcock
author_sort Shamila D. Alipoor
collection DOAJ
description Abstract Background 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). Methods 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. Results 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. Conclusions 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.
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spelling doaj.art-02c9870baa2a447bbdf53506e97ad1922022-12-21T20:11:09ZengBMCJournal of Translational Medicine1479-58762017-05-011511910.1186/s12967-017-1205-9Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophagesShamila D. Alipoor0Esmaeil Mortaz1Payam Tabarsi2Parissa Farnia3Mehdi Mirsaeidi4Johan Garssen5Masoud Movassaghi6Ian M. Adcock7Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical SciencesClinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical SciencesClinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical SciencesMycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical SciencesDivision of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of MiamiDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht UniversityDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA)Airways Disease Section, National Heart & Lung Institute, Imperial College LondonAbstract Background 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). Methods 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12967-017-1205-9MycobacteriumExosomemiRNAMacrophageBiomarker
spellingShingle Shamila D. Alipoor
Esmaeil Mortaz
Payam Tabarsi
Parissa Farnia
Mehdi Mirsaeidi
Johan Garssen
Masoud Movassaghi
Ian M. Adcock
Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages
Journal of Translational Medicine
Mycobacterium
Exosome
miRNA
Macrophage
Biomarker
title Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages
title_full Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages
title_fullStr Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages
title_full_unstemmed Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages
title_short Bovis Bacillus Calmette–Guerin (BCG) infection induces exosomal miRNA release by human macrophages
title_sort bovis bacillus calmette guerin bcg infection induces exosomal mirna release by human macrophages
topic Mycobacterium
Exosome
miRNA
Macrophage
Biomarker
url http://link.springer.com/article/10.1186/s12967-017-1205-9
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