microRNA Expression Profile and Response of Alveolar and Peritoneal Derived Macrophages to Mycobacterial Infection

Abstract

Tuberculosis (TB) is one of the devastating infectious diseases worldwide, with over 9 million new cases reported in 2013. Mycobacterium tuberculosis is the causative agent and it primarily infects lungs. Upon infection, lung macrophages are activated to contain the bacilli. The interaction between host macrophages and the bacilli determines the outcome of the disease. In 1993, the discovery of miRNAs has opened a new door to a deeper understanding on cell biology and the host inflammatory response against various diseases. Recent studies on miRNA have also revealed its importance during M. tuberculosis infection. This study investigated how mycobacterial infection modulates the miRNA expression profile in murine alveolar (AMJ2.C11) and peritoneal (IC-21) macrophage cell lines. The effect on bacterial virulence on miRNA expression was also examined by comparing infection with virulent M. tuberculosis and the vaccine strain M. bovis BCG. The result showed that different strain of Mycobacterium induced different miRNA expressions on both types of murine macrophage cell lines. Moreover, the pattern of bacterial killing was different on both types of cells. When a particular miRNA was knockdown, miR-146a chose in this study, AMJ2.C11 cells showed a reduction of bacterial load compared to IC-21 cells. This finding has opened a new path to further examine the significance of miRNAs including miR-146a in regulating host immunity to tuberculosis. Although further complex investigations need to be established, determining how miRNAs regulate immunity to M. tuberculosis may identify new targets for future therapeutic intervention.