miR-1224 Expression is Increased in Human Macrophage After Infection With Bacillus Calmette-Guerin (BCG)

Abstract

Introduction: Tuberculosis remains a major threat to human health. Understanding the strategies mycobacterium takes to overcome immune defense is important to control the infection. miRNAs are master regulators of most pathways in the human body. Infection with mycobacterium impacts upon host metabolic pathways to obtain the nutrition for its intracellular survival. In this study, we aimed to investigate the effect of BCG infection on the expression of three miRNAs (miR-1224, -484 and -425), which have been previously demonstrated to be important in infection and metabolic pathways. Methods: Blood-derived monocyte derived macrophage (MDM) cultures were prepared and infected with BCG at a multiplicity of infection (MOI) =10 or left uninfected as a control. 72h post-infection, the cultured cells were subjected to RNA extraction, cDNA synthesis and real-time PCR. Expression levels miRNAs were normalized to the levels of U6 snRNA (Rnu6) using the 2–ΔΔCt method Results: Infection with BCG resulted in a highly significant increase in miR-1224 expression (24.4±3.8-fold induction) in human MDMs. The induction of miR-484 (1.8±0.3-fold increase) and of miR-425 (1.2±0.2-fold increase) was less increased compared to miR-1224. Discussion: Mycobacterium tolerate an hostile microenvironment by escaping from lysosomal degradation and providing a lipid-rich niche by trigger with and re-pattering host metabolism. These data highlight the potential importance of miR-1224 in the host metabolic response to TB infection and a possible role of miR-484 in the reprogramming of metabolic pathways in infected cells. Further work is required to determine whether these miRNAs may also be useful as biomarkers for the diagnosis or monitoring of treatment in TB patients. Conclusion: This study Highlighted the potential roles of miRNAs in host immunologic responses upon mycobacterium infection. Further work is required to determine whether these miRNAs may also be useful as biomarkers for the diagnosis or monitoring of treatment in TB patients.