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Front. Microbiol. | doi: 10.3389/fmicb.2019.01174

Small RNA Profiles of Serum Exosomes Derived from Individuals with Latent and Active Tuberculosis

 Lingna Lvu1, Xiuli Zhang2, Cuidan Li2, Tingting Yang2, Jinghui Wang1,  Liping Pan1, Hongyan Jia1,  Zihui Li1, Qi Sun1, Liya Yue2,  Fei Chen3* and  Zongde Zhang1
  • 1Beijing Tuberculosis and Thoracic Tumor Research Institute, Department of Molecular Biology / Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, China
  • 2CAS Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, China
  • 3Beijing Institute of Genomics, Chinese Academy of Sciences, China

Tuberculosis (TB) has been the leading lethal infectious disease worldwide since 2014, and about one third of the world’s population has latent TB infection (LTBI). It is largely attributed to the difficulties in diagnosis and treatment of TB and LTBI patients. Exosomes offer a new perspective on investigation of the process of TB infection. In this study, we performed small RNA sequencing to explore small RNA profiles of serum exosomes derived from LTBI and TB patients and healthy controls (HC). Our results revealed distinct miRNA profile of the exosomes in the three groups. We screened 250 differentially expressed miRNAs including 130 specifically expressed miRNAs. Some miRNAs were further validated to be specifically expressed in LTBI (hsa-let-7e-5p, hsa-let-7d-5p, hsa-miR-450a-5p, hsa-miR-140-5p) and TB samples (hsa-miR-1246, hsa-miR-2110, hsa-miR-370-3P, hsa-miR-28-3p, hsa-miR-193b-5p). Besides, we demonstrated four expression panels in LTBI and TB groups, and six expression patterns among the three groups. These specifically expressed miRNAs and differentially expressed miRNAs in different panels and patterns provide potential biomarkers for detection/diagnosis of latent and active TB using exosomal miRNAs. Additionally, we also discovered plenty of small RNAs derived from genomic repetitive sequences, which might play roles in host immune responses along with Mtb infection progresses. Overall, our findings provide important reference and improved understanding about miRNAs and repetitive region-derived small RNAs in exosomes during the Mtb infectious process, and facilitate the development of potential molecular targets for detection/diagnosis of latent and active tuberculosis.

Keywords: exosome, miRNA, tuberculosis (TB), RNA sequencing, small RNA, Latent TB infection (LTBI)

Received: 20 Dec 2018; Accepted: 08 May 2019.

Edited by:

Feng Gao, Tianjin University, China

Reviewed by:

George Dubyak, Case Western Reserve University, United States
Seyed Davar Siadat, Pasteur Institute of Iran (PII), Iran
Zhenjun Li, Chinese Center For Disease Control and Prevention, China  

Copyright: © 2019 Lvu, Zhang, Li, Yang, Wang, Pan, Jia, Li, Sun, Yue, Chen and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Fei Chen, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China, chenfei@big.ac.cn