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. 2017 May 12;15(1):105.
doi: 10.1186/s12967-017-1205-9.

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

Shamila D Alipoor  1   2   3 , Esmaeil Mortaz  4   5   6 , Payam Tabarsi  1 , Parissa Farnia  7 , Mehdi Mirsaeidi  8 , Johan Garssen  9   10 , Masoud Movassaghi  11 , Ian M Adcock  12   13
Affiliations

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

Shamila D Alipoor et al. J Transl Med. .

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.

Keywords: Biomarker; Exosome; Macrophage; Mycobacterium; miRNA.

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Figures

Fig. 1
Fig. 1
Exosome characterization by scanning (SEM) and transmission electron microscopy (TEM) and nanoanalyzer. Exosomes were isolated by total exosome isolation reagents and passed twice through a 0.22 mm filter before being analyzed for morphology by SEM (a) and TEM (b). The size distribution of the isolated exosomes was further analyzed by nanoanalyzer (c) and showed the size distribution of the exosomes as 70 ± 3.4 nm. The results are representative of three independent experiments
Fig. 2
Fig. 2
Exosomal RNA qualification. Total RNA was extracted from the exosomes and the quality of the exosomal RNA was assessed by running the samples on an Agilent Bioanalyzer. The RNA population observed in the exosomes were predominantly from small RNAs. The result is representative of three independent experiments
See this image and copyright information in PMC

References

    1. Kruh-Garcia NA, Wolfe LM, Dobos KM. Deciphering the role of exosomes in tuberculosis. Tuberculosis. 2015;95(1):26–30. doi: 10.1016/j.tube.2014.10.010. - DOI - PubMed
    1. Organization, W.H. Global tuberculosis report 2015. Geneva: World Health Organization; 2015.
    1. Person AK, Pettit AC, Sterling TR. Diagnosis and treatment of latent tuberculosis infection: an update. Curr Respir Care Rep. 2013;2(4):199–207. doi: 10.1007/s13665-013-0064-y. - DOI - PMC - PubMed
    1. Tsara V, Serasli E, Christaki P. Problems in diagnosis and treatment of tuberculosis infection. Hippokratia. 2009;13(1):20. - PMC - PubMed
    1. Davies P, Pai M. The diagnosis and misdiagnosis of tuberculosis. [State of the art series. Tuberculosis. Edited by ID Rusen. Number 1 in the series] Int J Tuberc Lung Dis. 2008;12(11):1226–1234. - PubMed

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