miRNAs in Tuberculosis: New Avenues for Diagnosis and Host-Directed Therapy

Abstract

Tuberculosis (TB) is one of the most fatal infectious diseases and a leading cause of mortality, with 95% of these deaths occurring in developing countries. The causative agent, Mycobacterium tuberculosis (Mtb), has a well-established ability to circumvent the host’s immune system for its intracellular survival. microRNAs (miRNAs) are small, non-coding RNAs having an important function at the post-transcriptional level and are involved in shaping immunity by regulating the repertoire of genes expressed in immune cells. It has been established in recent studies that the innate immune response against TB is significantly regulated by miRNAs. Moreover, differential expression of miRNA in Mtb infection can reflect the disease progression and may help distinguish between active and latent TB infection (LTBI). These findings encouraged the application of miRNAs as potential biomarkers. Similarly, active participation of miRNAs in modulation of autophagy and apoptosis responses against Mtb opens an exciting avenue for the exploitation of miRNAs as host directed therapy (HDT) against TB. Nanoparticles mediated delivery of miRNAs to treat various diseases has been reported and this technology has a great potential to be used in TB. In reality, this exploitation of miRNAs as biomarkers and in HDT is still in its infancy stage, and more studies using animal models mimicking human TB are advocated to assess the role of miRNAs as biomarkers and therapeutic targets. In this review, we attempt to summarize the recent advancements in the role of miRNAs in TB as immune modulator, miRNAs’ capability to distinguish between active and latent TB and, finally, usage of miRNAs as therapeutic targets against TB.

The role of host miRNAs on Mycobacterium tuberculosis

“…Autophagy is an intracellular process involved in self-digestion or self-eating, in which cytoplasmic components are transmitted to the lysosome and are ultimately degenerated [82]. The pathways associated with autophagy are challenging to regulate at post-transcriptional levels and are well described, but the involvement of miRNAs inactivating or inhibiting autophagy during TB infection is largely unknown [30]. Some reports show the induction of the miR-33 expression in THP-1 and HEK-293 cells, leading to inhibition of pathways involved in autophagy, and also resulting in reprogramming of host lipid metabolism for intracellular survival and TB stability [30].…”

“…MiRNAs are the main regulator of cell differentiation and cell functions, as well as modulators in most cellular functions, including innate and acquired immune systems [27,28]. For example, acquired immune responses, B cell differentiation, antibody production, T cell development, and function are controlled by miRNAs [29], and many studies describe the role of mammalian miRNAs in response to bacterial infections [30]. M. tuberculosis is an intracellular pathogen and can survive within the host macrophages.…”

The Relationship Between the miRNA Sequence and Disease May be Revealed by Focusing on Hydrogen Bonding Sites in RNA–RNA Interactions

“…Currently, it is estimated that one-third of the world's population is potentially infected. However, it affects about 5-10% of infected people [5].…”

miRNA Expression Profiles and Potential as Biomarkers in Nontuberculous Mycobacterial Pulmonary Disease

“…Because of their high diagnostic potential, open Scientific RepoRtS | (2020) 10:3178 | https://doi.org/10.1038/s41598-020-60132-0www.nature.com/scientificreports www.nature.com/scientificreports/ serum miRNAs have been evaluated as biomarkers in several pathological conditions including TB, with some studies achieving 82% to 100% accuracy in diagnosing TB by evaluating miRNA [13][14][15][16][17][18] . Additionally, several studies have reported differences in miRNA levels among patients with active TB, latent TB, and healthy controls 18,19 . Recently, the roles of miRNAs in mycobacterial infections, particularly in tuberculosis (TB), has received increasing attention 13,20-23 Such studies have reported that specific miRNAs are differentially expressed in macrophages or patients infected with M. tuberculosis complex and that several of these miRNAs interact with their cognate target genes.…”