Unraveling the Role of MicroRNAs in Mycobacterium tuberculosis Infection and Disease: Advances and Pitfalls

Abstract

Tuberculosis (TB) is an infectious disease of extremely high epidemiological burden worldwide that is easily acquired through the inhalation of infected respiratory droplets. The complex pathogenesis of this infection spans from subjects never developing this disease despite intense exposure, to others in which immune containment fails catastrophically and severe or disseminated forms of disease ensue. In recent decades, microRNAs (miRNAs) have gained increasing attention due to their role as gene silencers and because of their altered expression in diverse human diseases, including some infections. Recent research regarding miRNAs and TB has revealed that the expression profile for particular miRNAs clearly changes upon Mycobacterium tuberculosis infection and also varies in the different stages of this disease. However, despite the growing number of studies—some of which have even proposed some miRNAs as potential biomarkers—methodological variations and key differences in relevant factors, such as sex and age, cell type analyzed, M. tuberculosis strain, and antimicrobial therapy status, strongly hinder the comparison of data. In this review, we summarize and discuss the literature and highlight the role of selected miRNAs that have specifically and more consistently been associated with M. tuberculosis infection, together with a discussion of the possible gene and immune regulation pathways involved.

Regulatory Mechanisms of Autophagy-Targeted Antimicrobial Therapeutics Against Mycobacterial Infection

“…However, ATGs, except ATG5, in myeloid cells do not appear to be essential in the activation of host defense in vivo ( Kimmey et al., 2015 ). In addition, Mtb pathogens can epigenetically control host autophagy pathway through regulation of microRNAs (miRNAs) to favor mycobacterial replication in the host cells during infection ( Batista et al., 2020 ; Ruiz-Tagle et al., 2020 ; Silwal et al., 2020 ). The miRNAs that are associated with pathogenesis of Mtb infection include miR-33/miR-33* ( Ouimet et al., 2016 ), miR-889 ( Chen et al., 2020 ), miR-18a ( Yuan et al., 2020 ), and miR-125a ( Kim et al., 2015 ), all of which are increased by Mtb infection; whereas others such as miR-26a ( Sahu et al., 2017 ) and miR-17-5p ( Kumar et al., 2016 ), both of which are decreased by Mtb infection.…”

Pediatric Tuberculosis: The Impact of “Omics” on Diagnostics Development

“…Using miRNA as a marker was found to have an overall sensitivity of 86% and a 79% specificity for diagnosis of active TB infection in these varied populations. Using RNA sequencing of whole blood samples, researchers examined the use of small non-coding RNA population such as miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) as host biomarkers for active and latent MTB in a systematic manner [ 86 , 87 ]. From this approach, one miRNA and two piRNAs were identified as potential biomarkers for latent MTB [ 88 ], but further studies are required for their validation in such an application.…”

Granulomatosis in fish aquaculture: a mini review

“…For example, Ruiz‐Tagle et al . (2020) documented a non‐necrotic granuloma consisting predominantly of lymphocytes, macrophages, giant cells and produced by mycobacteria. However, the granuloma progressed to a necrotic state registering changes in its microenvironment, macrophage apoptosis and the bacteria slowing their growth rate.…”