Can miRNA Indicate Risk of Illness after Continuous Exposure to M. tuberculosis?

SIMPLE SUMMARY: Tuberculosis is the leading cause of mortality from a single infectious agent and is among the top 10 causes of death worldwide. Despite that, few studies focus on regulatory elements such as small non-coding RNAs in tuberculosis. This pilot work applied Next Generation Sequencing techniques to evaluate the global miRNA expression profile of patients with active tuberculosis; their respective healthy physicians, who are at constant risk of infection; and a second group of healthy controls. In addition, we observed miRNA–gene interactions affected by exposure to the bacteria. Our findings indicate a list of miRNAs that could be used as potential biomarkers to improve treatment strategies at early stages. We also observed modified pathways related to the immune response due to differential miRNA expression profiles. Finally, we alert and encourage the development of new strategies to avoid long-term exposure of healthy physicians, considering how closely related their miRNA profile was to tuberculosis patients using current safety protocols. ABSTRACT: The role of regulatory elements such as small ncRNAs and their mechanisms are poorly understood in infectious diseases. Tuberculosis is one of the oldest infectious diseases of humans and it is still a challenge to prevent and treat. Control of the infection, as well as its diagnosis, are still complex and current treatments used are linked to several side effects. This study aimed to identify possible biomarkers for tuberculosis by applying NGS techniques to obtain global miRNA expression profiles from 22 blood samples of infected patients with tuberculosis (n = 9), their respective healthy physicians (n = 6) and external healthy individuals as controls (n = 7). Samples were run through a pipeline consisting of differential expression, target genes, gene set enrichment and miRNA–gene network analyses. We observed 153 altered miRNAs, among which only three DEmiRNAs (hsa-let-7g-5p, hsa-miR-486-3p and hsa-miR-4732-5p) were found between the investigated patients and their respective physicians. These DEmiRNAs are suggested to play an important role in granuloma regulation and their immune physiopathology. Our results indicate that miRNAs may be involved in immune modulation by regulating gene expression in cells of the immune system. Our findings encourage the application of miRNAs as potential biomarkers for tuberculosis.