Small RNA Profiles of Serum Exosomes Derived From Individuals With Latent and Active Tuberculosis

Abstract

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.

Evaluation of digital PCR assay in detection of M.tuberculosis IS6110 and IS1081 in tuberculosis patients plasma

“…TB was about 90% according to a meta-analysis of newly reported evidence from 20 studies [27]. Furthermore, we and other groups have illustrated that there were M.tuberculosis nucleic acids in exosomes derived from plasma of both patients and healthy specimens as well as M.tuberculosis non-infected macrophages in vitro [28][29][30]. Considering the DNA extraction method we used here, the detected sequences in plasma may include bacterium genome DNA, circulating DNA as well as exosomal DNA.…”

Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers

“…In this cohort, expression levels of miRNAs was similar in subjects co-infected with HIV and in those without HIV infection [ 86 ]. A recent study in China, which analyzed miRNA expression profile by RNA-sequencing in serum exosomes, found overexpression of miR-1246, miR-2110, miR-370-3p, miR-28-3p, miR-193b-5p and downregulation of miR-3675-5p in active TB, but also identified a set of miRNAs exclusively expressed in latent TB [ 85 ]. No validation experiments in a second cohort of patients were performed.…”

Immune Biomarkers for Diagnosis and Treatment Monitoring of Tuberculosis: Current Developments and Future Prospects

“…miRNA has also been used to differentiate LTBI from active TB. By studying 250 miRNAs, Lyu et al (2019) also identified the patterns where the hsa-let-7e-5p, hsa-let-7d-5p, hsa-miR-450a-5p, and has-miR-140-5p were differentially expressed among patients with LTBI; whilst hsa-miR-1246, hsa-miR-2110, hsa-miR-370-3p, hsa-miR-28-3p, hsa-miR-193b-5p were associated differentially expressed among patients with active TB.…”