National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran TANAFFOS (Respiration) 1735-0344 21 4 2022 10 01 Extracellular Vesicles from Serum of Mycobacteria Patients Accelerate Expression of Apoptosis miRNAs and Facilitate THP-1 Monocyte Cell Death 434 447 706530 EN Alireza Javadi Virology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 0000-0001-9970-5470 Masoud Shamaei Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 0000-0002-1991-0536 Payam Tabarsi Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 0000-0002-8932-5420 Elaheh Ainy Safety Promotion and Injury Prevention Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 0000-0002-6423-0310 Bahram Kazemi Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 0000-0002-3072-8831 Journal Article 2022 01 08 <strong>Background: </strong>Extracellular vesicles<strong> (</strong>EVs) may accelerate cell death during the course of infection. Mycobacteria could invade the host’s immune system and survive in the host by modulation of miRNAs. MiRNAs' differential expressions can serve as biomarkers. This study evaluates THP-1 monocyte cell death by EVs from serum of patients with mycobacteria and assesses serum-derived exosomal miRNAs to increase or decrease THP-1 monocyte cell death.<br /><strong>Materials and Methods: </strong>EVs were purified from serum of patients with mycobacteria and cultured with THP-1 monocyte. The cell death was determined via annexin V-FITC and PI staining. The microRNA was isolated from serum-derived EVs of the patients. Expression level of Hsa-miR-20a-5p, Hsa-miR-29a, Hsa-miR-let7e, and Hsa-miR-155 was assessed using qRT-PCR.<br /><strong>Results: </strong>Cell death was accelerated in 10 and 5 µg/ml concentrations of the EVs (p<0.05). Minimum cell death was seen in 2.5 and 1.2 µg/ml concentrations (p<0.05). In tuberculosis (TB) patients, expression of miR-20a-5p, miR-29a, and miR-let7e were significantly enhanced (p≤0.0001), but miR-155 expression reduced. ROC analysis showed diagnostic biomarkers of miRNAs with an AUC=0.6933 for miR-20, AUC=0.6011 for miR-29a, AUC=0.7322 for miR-let7e, and AUC=0.7456 for miR-155 for active tuberculosis. Expression of miR-let7e, 20a, and 29a in <em>M. avium</em> vs. <em>M.</em> <em>tuberculosis </em>was overexpressed (P≤0.01, P≤0.0001, and P≤0.0001, respectively). Also miRs let7e and 20a expression was accelerated in <em>M. abscessus</em> vs. <em>M. tuberculosis </em>(P≤0.0001 and P≤0.002, respectively).<br /><strong>Conclusion:</strong> EVs accelerates cell death and may not be ideally considered for drug delivery and vaccine developments. Circulating exosomal microRNA MiR-20, miR-let7e, and miR-155 facilitate development of potential biomarkers of pulmonary tuberculosis and non-tuberculosis. https://www.tanaffosjournal.ir/article_706530_d1091fcbc878044e40227a8bca4607b9.pdf