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

Alipoor, Shamila D.; Mortaz, Esmaeil; Tabarsi, Payam; Farnia, Parissa; Mirsaeidi, Mehdi; Garssen, Johan; Movassaghi, Masoud; Adcock, Ian M.

doi:10.1186/s12967-017-1205-9

Cited by 60 publications

(80 citation statements)

References 68 publications

(81 reference statements)

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“…These would include CD9, CD63, and CD81 if the exosome was endosomal in origin [ 8 ]. Exosomes can, therefore, significantly affect target cell function resulting in the development of a pathological state [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Exosomes in Severe Asthma: Update in Their Roles and Potential in Therapy

Mortaz

Alipoor

Varahram

et al. 2018

BioMed Research International

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Exosomes are nanosized vesicles and have recently been recognized as important players in cell-to-cell communication. Exosomes contain different mediators such as proteins, nucleic acids (DNA, mRNA, miRNAs, and other ncRNAs), and lipid mediators and can shuttle their exosomal content to both neighboring and distal cells. Exosomes are very effective in orchestrating immune responses in the airways and all cell types can contribute to the systemic exosome pool. Intracellular communication between the broad range of cell types within the lung is crucial in disease emphasizing the importance of exosomes. In asthma, exosomes affect the inflammatory microenvironment which ultimately determines the development or alleviation of the pathological symptoms. Recent studies in this area have provided insight into the underlying mechanisms of disease and led to interest in using exosomes as potential novel therapeutic agents.

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Section: Introductionmentioning

confidence: 99%

Exosomes in Severe Asthma: Update in Their Roles and Potential in Therapy

Mortaz

Alipoor

Varahram

et al. 2018

BioMed Research International

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“…39 Likewise, upon infection of macrophages with Mycobacterium bovis Bacillus Calmette-Guerin (BCG), the miRNA content of macrophage-derived exosomes is altered. 40 In silico analysis suggested that the differentially expressed exosomal miRNAs may subvert host metabolic pathway to enable BCG survival within infected macrophages. 40 Evidence has also suggested that extracellular vesicles, which include exosomes, seem to play a role in IBD.…”

Section: Discussionmentioning

confidence: 99%

“…40 In silico analysis suggested that the differentially expressed exosomal miRNAs may subvert host metabolic pathway to enable BCG survival within infected macrophages. 40 Evidence has also suggested that extracellular vesicles, which include exosomes, seem to play a role in IBD. The extracellular vesicles purified from the intestinal lumen of IBD patients convey a higher amount of IL-6, IL-8, IL-10 and TNF-α compared to those from healthy subjects, and the levels of these pro-inflammatory mediators were positively correlated with CD severity score.…”

Section: Discussionmentioning

confidence: 99%

Exosomes transfer miRNAs from cell-to-cell to inhibit autophagy during infection with Crohn’s disease-associated adherent-invasive E. coli

et al. 2020

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Adherent-invasive E. coli (AIEC), which abnormally colonize the intestinal mucosa of Crohn's disease (CD) patients, are able to adhere to and invade intestinal epithelial cells (IECs), survive and replicate within macrophages and induce a pro-inflammatory response. AIEC infection of IECs induces secretion of exosomes that increase AIEC replication in exosome-receiving IECs and macrophages. Here, we investigated the mechanism underlying the increased AIEC replication in cells receiving exosomes from AIEC-infected cells. Exosomes released by uninfected human intestinal epithelial T84 cells (Exo-uninfected) or by T84 cells infected with the clinical AIEC LF82 strain (Exo-LF82), the nonpathogenic E. coli K12 strain (Exo-K12) or the commensal E. coli HS strain (Exo-HS) were purified and used to stimulate T84 cells. Stimulation of T84 cells with Exo-LF82 inhibited autophagy compared with Exo-uninfected, Exo-K12 and Exo-HS. qRT-PCR analysis revealed increased levels of miR-30c and miR-130a in Exo-LF82 compared to Exo-uninfected, Exo-K12 and Exo-HS. These miRNAs were transferred via exosomes to recipient cells, in which they targeted and inhibited ATG5 and ATG16L1 expression and thereby autophagy response, thus favoring AIEC intracellular replication. Inhibition of these miRNAs in exosome-donor cells infected with AIEC LF82 abolished the increase in miR-30c and miR-130a levels in the released Exo-LF82 and in Exo-LF82-receiving cells, thus suppressing the inhibitory effect of Exo-LF82 on ATG5 and ATG16L1 expression and on autophagy-mediated AIEC clearance in Exo-LF82-receiving cells. Our study shows that upon AIEC infection, IECs secrete exosomes that can transfer specific miRNAs to recipient IECs, inhibiting autophagy-mediated clearance of intracellular AIEC.

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“…Previous studies reported that miRNA-625-3p in the blood facilitated the detection of malignancy in benign lung tumors 34 , and miRNA-625-3p is reportedly upregulated in the urine of pulmonary TB patients and is an excellent diagnostic urinary biomarker 35 . miR-4732-3p is associated with breast cancer and stomach cancer and is specifically expressed in exosomes released from macrophages after infection with BCG 20,36 . We hypothesized that differential expression of these miRNAs in patients with NTM-PD and healthy controls would result in differences of target mRNA expression; thus, additional experimental validation is further required.…”

Section: Discussionmentioning

confidence: 99%

miRNA Expression Profiles and Potential as Biomarkers in Nontuberculous Mycobacterial Pulmonary Disease

Han

Jhun

Kim

et al. 2020

Sci Rep

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Pulmonary disease (PD) due to nontuberculous mycobacteria (NTM) is increasing globally, but specific biomarkers for NTM-PD have not been established. As circulating miRNAs are promising biomarkers for various diseases, we investigated whether miRNAs have potential as NTM-PD biomarkers. Sera from 12 NTM-PD patients due to Mycobacterium avium, M. intracellulare, M. abscessus, or M. massiliense and three healthy controls were initially evaluated via small RNA sequencing. Multiple miRNAs showed significant differences in expression in patients compared to in healthy controls, with some expression differences unique to PD caused by a specific mycobacterial species. Notably, 14 miRNAs exhibited significant expression differences in PD associated with all four mycobacteria. Validation by quantitative reverse-transcription-PCR in an additional 40 patients with NTM-PD and 40 healthy controls confirmed that four differentially expressed miRNAs (hsa-miR-484, hsa-miR-584-5p, hsa-miR-625-3p, and hsa-miR-4732-5p) showed significantly higher serum expressions in NTM-PD patients than in controls. Receiver operating characteristic curve analysis of these four miRNAs supported the discriminative potential for NTM-PD and their combination provided an improved diagnostic value for NTM-PD. Furthermore, bioinformatics analysis revealed their 125 target genes, which were mostly associated with immune responses. Collectively, this study identified four miRNAs as potential biomarkers for NTM-PD and provided insight into NTM-PD pathophysiology.Nontuberculous mycobacteria (NTM) are mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. More than 180 officially recognized NTM species have been identified, with the most frequent human pathogens associated with pulmonary disease (PD) due to NTM belonging to the Mycobacterium avium complex (MAC), followed by M. abscessus (MAB) 1,2 . MAC primarily comprises M. avium and M. intracellulare, and MAB primarily comprises M. abscessus subspecies abscessus (hereafter referred to as M. abscessus) and M. abscessus subspecies massiliense (hereafter referred to as M. massiliense) 1,2 . Despite the global increase in the burden of NTM-PD in recent decades, there is limited information regarding specific biomarkers for distinguishing patients with NTM-PD from healthy individuals or studies of the disease pathophysiology 3,4 .MicroRNAs (miRNAs) are small, 18-25-nucleotide, endogenous, stable, highly conserved noncoding RNAs with important functions in post-transcriptional gene regulation under both physiological and pathological conditions 5,6 . Numerous studies have reported the aberrant expression of several miRNAs in various conditions, including cancer and infectious diseases. miRNAs reportedly play an important regulatory role in the pathogenesis or progression of infectious diseases 7,8 and serve as potential modulators of innate and adaptive immune responses 9,10 . Serum miRNAs are not readily degraded by enzymes, unaffected by changes in temperature and time, and res...

show abstract

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

Cited by 60 publications

References 68 publications

Exosomes in Severe Asthma: Update in Their Roles and Potential in Therapy

Exosomes in Severe Asthma: Update in Their Roles and Potential in Therapy

Exosomes transfer miRNAs from cell-to-cell to inhibit autophagy during infection with Crohn’s disease-associated adherent-invasive E. coli

miRNA Expression Profiles and Potential as Biomarkers in Nontuberculous Mycobacterial Pulmonary Disease

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