Role of the immunoregulatory microRNA miR-146a in the innate immune response to rhinovirus infection

MicroRNAs are increasingly recognized as key regulators of the immune response, including innate immunity to viral infections. A key step in the induction of an antiviral state is the production of interferon-beta (IFNb). MiR-146a has been previously described to control expression levels of TRAF6, a signaling molecule involved in the expression of IFNb. In this project we sought to evaluate the relevance of miR-146a in regulating the innate antiviral response to human rhinovirus (HRV), one of the major triggers of acute exacerbations of chronic lung diseases. As a model of HRV infection, two airway epithelial cell lines of distinct anatomical origin and different basal expression of miR-146a were infected with HRV16. For functional analysis, we inhibited miR-146a function in these cell lines by transfection with specific inhibitors. In 16-HBE cells, expression of miR-146a did not change after infection with HRV, whereas it was significantly increased in A549 cells upon infection. Since this up-regulation might hamper the cells’ response to the virus, we next investigated whether inhibition of miR-146a enhances the production of IFNb. Despite successful transfection, inhibition of miR-146a did not alter the production of IFNb upon HRV infection. Moreover, and in contrast to previous reports, levels of the miR-146a target TRAF6 were not affected by inhibition of miR-146a.Taken together, our data question the importance of miR-146a in regulating the type I IFN response in respiratory epithelial cells. Due to the complexity of microRNA functions, their role in orchestrating the immune response to respiratory infections still remains a promising subject for further studies.