RNA Profiling Analysis of the Serum Exosomes Derived from Patients with Active and Latent Mycobacterium tuberculosis Infection.

Xinmiao Jia,Tianshu Cao,Nan Ding,Xiuli Zhang,Hongyan Jia,Zihui Li,Jinghui Wang,Zongde Zhang,Liping Pan,Ju Zhang,Lingna Lv,Cuidan Li,Fei Chen

doi:10.3389/fmicb.2017.01051

Abstract

Tuberculosis (TB) has exceeded HIV as the most lethal infectious disease globally for two consecutive years. Moreover, one third of the world’s population is estimated to have latent tuberculosis infection (LTBI). This is mainly because of difficulties associated with diagnosis and treatment for both TB and LTBI patients. Exosomes provide a promising research tool for TB diagnosis and treatment because they are released from various cells containing valuable biochemical information related to disease. In this study, we performed RNA-sequencing analysis on exosomes derived from clinical specimens of healthy controls (HC), active tuberculosis (ATB), and LTBI patients. Our results revealed the distinct gene expression profiles of the exosomes from LTBI and ATB patients. (1) We identified many distinct up-regulated and down-regulated differentially expressed genes (DEGs) in LTBI and ATB samples, and further screened the top-20 DEGs which might provide a potential panel for differentiation of HC, LTBI, and ATB. (2) We classified all the DEGs into six expression patterns, screened the top-20 genes in each pattern, and mainly focused on those highly expressed in LTBI and ATB. (3) Some Mycobacterium tuberculosis (Mtb) RNAs were only enriched in the exosomes of LTBI samples. (4) Pathway and function analysis further indicated down-regulated signaling pathways/immune response and up-regulated apoptosis/necrosis. Our findings indicate the selective packaging of RNA cargoes into exosomes under different stages of Mtb infection, while facilitating the development of potential targets for the diagnosis, prevention and treatment of tuberculosis.

Highlights

According to the 2015 and 2016 WHO reports, tuberculosis has exceeded HIV as the most lethal infectious disease globally for two consecutive years (2014 and 2015)
(1) We identified many distinct up-regulated and down-regulated differentially expressed genes (DEGs) in latent tuberculosis infection (LTBI) and active tuberculosis (ATB) samples, and further screened the top-20 DEGs which might provide a potential panel for differentiation of healthy control (HC), LTBI, and ATB. (2) We classified all the DEGs into six expression patterns, screened the top-20 genes in each pattern, and mainly focused on those highly expressed in LTBI and ATB. (3) Some Mycobacterium tuberculosis (Mtb) RNAs were only enriched in the exosomes of LTBI samples
We revealed distinct gene expression panels and patterns of serum exosomes from three groups, which included healthy, latently infected and actively infected TB individuals

Summary

Introduction

According to the 2015 and 2016 WHO reports, tuberculosis has exceeded HIV as the most lethal infectious disease globally for two consecutive years (2014 and 2015). This is mainly because of difficulties associated with diagnosis and treatment of TB patients. Elimination of tuberculosis has been partly prevented by the ability of Mtb to remain dormant in the human body for years without causing disease, a state referred to as LTBI (Velayati et al, 2016). Early diagnosis of LTBI patients plays a crucial and important role in reducing morbidity, while preventing onward transmission to susceptible individuals

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Results

Conclusion