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.
Highlights
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the most fatal infectious diseases (Dye and Williams, 2010)
TNF biosynthesis is inhibited by miR-125b in Mtb-infected human alveolar macrophages (Rajaram et al, 2011). miR-29 helps control innate and adaptive immune responses against Mtb by targeting interferon-γ and it is suggested as a biomarker for pulmonary tuberculosis because it is related to the clinical manifestation of the disease (Ma et al, 2011)
Tuberculosis (TB) is one of the world’s most deadly communicable diseases and Mtb is difficult to eradicate, due to its capability to persist within macrophages
Summary
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the most fatal infectious diseases (Dye and Williams, 2010). Many research groups have reported the differential expression of miRNAs in host cells challenged with Mtb, indicating the important role of these miRNAs in regulating the immune response in TB and proposing the miRNAs as potential biomarkers (Wang et al, 2011; Qi et al, 2012; Wu et al, 2012; Zhang et al, 2013). Lipomannan from virulent Mtb stimulated the expression of miR-125b in human macrophages while lipomannan from avirulent M. smegmatis -resulted in increased expression of miR-155 (Rajaram et al, 2011) These reports revealed that components from related bacterial species, with different virulence, lead to differential expression of miRNAs and modulated the immune response. The results suggested that TF-miRNA gene co-regulatory networks may help provide a miRNAs in Tuberculosis
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