Abstract

ObjectivesThe role of microRNAs in association with Mycobacterium tuberculosis (MTB) infection and the immunology regulated by microRNAs upon MTB infection have not been fully unravelled. We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of Beijing/W and non-Beijing/W clinical strains. We also studied the microRNA profiles of the host macrophages by microarray in a small cohort with active MTB disease, latent infection (LTBI), and from healthy controls.ResultsThe results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (P<0.05). A unique signature of 11 microRNAs in human macrophages was identified to differentiate active MTB disease from LTBI and healthy controls. Pathway analyses of these differentially expressed miRNAs suggest that the immune-regulatory interactions involving TGF-β signalling pathway take part in the dysregulation of critical TB processes in the macrophages, resulting in active expression of both cell communication and signalling transduction systems.ConclusionWe showed for the first time that the Beijing/W TB strains repressed a number of miRNAs expressions which may reflect their virulence characteristics in altering the host response. The unique signatures of 11 microRNAs may deserve further evaluation as candidates for biomarkers in the diagnosis of MTB and Beijing/W infections.

Highlights

  • Tuberculosis is one of the most common causes of death from infectious diseases

  • The results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (P

  • We showed for the first time that the Beijing/W TB strains repressed a number of miRNAs expressions which may reflect their virulence characteristics in altering the host response

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Summary

Introduction

Tuberculosis is one of the most common causes of death from infectious diseases. Studies have shown that one-third of the world’s population is infected with M. tuberculosis (MTB). The people who are infected with MTB but who do not have active tuberculosis have latent infection (LTBI), and they have a 10% lifetime chance that they will progress to having the active disease. Macrophages play a key role in the immune defence, and in particular, early clearance of MTB. MTB invade and replicate within alveolar macrophages. They evade the host defence system by blocking the formation of the apoptotic envelope [1] or inhibiting plasma membrane repair [2], which lead to macrophage necrosis and dissemination of infection in the lung

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