Tuberculosis (TB) is a major human pathogen, with over 8.6 million new cases reported in 2013. TB is acquired as a respiratory infection with lung macrophages the primary host cell infected. Activation of these macrophages is essential to contain the bacilli. Recent evidence has shown that microRNAs regulate the activation of many macrophage genes, but the influence of TB infection on miRNA expression is not well defined. We examined the effect on miRNA expression on infection with virulent M. tuberculosis compared with the vaccine strain M. bovis BCG in both human and murine macrophages.
In general M. tuberculosis infection induced an earlier and more robust miRNA expression, regardless of the cell type infected, compared with M. bovis BCG. IC-21 peritoneal macrophages showed maximal miRNA expression for the miRs -146, -155, -29, -99 and -221 by 6 hrs post infection with all the miRs bar -155 returning baseline by 24hrs. In contrast AMJ alveolar macrophages showed only minimal upregulation at 6 hrs with levels of all the miRs significantly elevated by 24 hrs post infection. This response was dose dependent with higher MOIs inducing more miR expression in both the IC-21 and AMJ cells. A similar response was seen in human monocyte derived macrophages (MDM) compared to human lung macrophages demonstrating that alveolar macrophages do not respond to mycobacterial infection in as rapid a timeframe as MDM. Studies are underway to examine the effect of individual miRs on regulating bacterial growth and the inflammatory response induced by mycobacterial infection.