MicroRNAs mediated-regulation of mycobacteria-induced cytokines production

Abstract

Tuberculosis (TB) is generally acquired through inhalation of airborne droplets containing Mycobacterium tuberculosis (Mtb). Macrophages are one of the pivotal cells in innate immunity against mycobacteria. Mycobacteria activate macrophages to produce proinflammatory cytokines such as TNF-α which controls Mtb infection. The cytokine is crucial for granuloma formation, induction of macrophage apoptosis and production of chemokines to recruit cells in tuberculosis. TNF-α biosynthesis is known to be controlled at the transcriptional and post-transcriptional levels. Emerging studies have shown that microRNAs (miRNAs), a family of single stranded, non-coding, short RNAs, act as post-transcriptional regulators of gene expressions. MiRNA-mediated regulations are essential in various developmental and cellular processes including tumor development and immune responses. MiRNAs regulate innate immunity and shape adaptive immunity. They target mRNAs of toll-like receptors (TLR), cellular signaling molecules, transcription factors or cytokines as to regulate the immunity. In this study, it was shown that various miRNAs were induced in primary human macrophages by Bacille Calmette-Guerin (BCG), a vaccine for TB. MiR-1303, which has not been shown to have function, was found to regulate BCG-induced TNF-α mRNA and protein production. It was shown that by knock-down of miR-1303, BCG-induced TNF-α protein expression was upregulated. In contrast, overexpression of miR-1303 can suppress the TNF-α protein expression. Additionally, it was demonstrated that miR-1303 could control levels of phosphorylated extracellular-signal-regulated kinase (ERK) and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK). Further studies on the mechanisms of the regulation will be required and the studies will delineate how miRNAs manipulate immune responses to mycobacteria infection.

Copyright © 2013 Published by Elsevier Ltd.