Small RNA Profiles of Serum Exosomes Derived From Individuals With Latent and Active Tuberculosis
Small RNA Profiles of Serum Exosomes Derived From Individuals With Latent and Active Tuberculosis
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潜伏性和活动性结核病患者血清外泌体的小 RNA 谱
DOI：
10.3389/fmicb.2019.01174
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发表时间：
2019-05-28
影响因子：
5.2
通讯作者：
Zhang, Zongde
中科院分区：
文献类型：
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作者：
Lyu, Lingna;Zhang, Xiuli;Zhang, Zongde
自2014年以来，结核病（TB）一直是全球主要的致命传染病，全球约三分之一的人口患有潜伏性结核病感染（LTBI）。这在很大程度上归因于结核病和LTBI患者的诊断和治疗困难。外泌体为研究结核病感染过程提供了新的视角。在这项研究中，我们进行了小RNA测序，以探索来自LTBI和TB患者和健康对照（HC）的血清外泌体的小RNA谱。我们的研究结果揭示了三组中外泌体的不同miRNA谱。我们筛选了250个差异表达的miRNAs，其中包括130个特异性表达的miRNAs。进一步验证了一些miRNA在LTBI（hsa-let-7 e-5 p、hsa-let-7 d-5 p、hsa-miR-450 a-5 p和hsa-miR-140- 5 p）和TB样品（hsa-miR-1246、hsa-miR-2110、hsa-miR-370- 3 P、hsa-miR-28- 3 p和hsa-miR-193 b-5 p）中特异性表达。此外，我们证明了LTBI和TB组中的四个表达组，以及三组中的六种表达模式。这些以不同的组和模式特异性表达的miRNA和差异表达的miRNA提供了使用外来体miRNA检测/诊断潜伏性和活动性TB的潜在生物标志物。此外，我们还发现了大量来自基因组重复序列的小RNA，这些小RNA可能随着结核分枝杆菌感染的进展而沿着参与宿主的免疫应答。总体而言，我们的研究结果提供了重要的参考，并提高了对Mtb感染过程中外泌体中miRNA和重复区域衍生的小RNA的理解，并促进了潜在的分子靶标的开发，用于检测/诊断潜伏性和活动性结核病。
Tuberculosis (TB) has been the leading lethal infectious disease worldwide since 2014, and about one third of the world's population has a latent TB infection (LTBI). This 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, and hsa-miR-140-5p) and TB samples (hsa-miR-1246, hsa-miR-2110, hsa-miR-370-3P, hsa-miR-28-3p, and hsa-miR-193b-5p). Additionally, 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 an 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.