Mycobacterium tuberculosis–induced IFN-β production requires cytosolic DNA and RNA sensing pathways

RNA sensing pathways are key elements in a host immune response to viral pathogens, but little is known of their importance during bacterial infections. We found that Mycobacterium tuberculosis (M.tb) actively releases RNA into the macrophage cytosol using the mycobacterial SecA2 and ESX-1 secretion systems. The cytosolic M.tb RNA induces IFN-β production through the host RIG-I/MAVS/IRF7 RNA sensing pathway. The inducible expression of IRF7 within infected cells requires an autocrine signaling through IFN-β and its receptor, and this early IFN-β production is dependent on STING and IRF3 activation. M.tb infection studies using Mavs−/− mice support a role for RNA sensors in regulating IFN-β production and bacterial replication in vivo. Together, our data indicate that M.tb RNA is actively released during an infection and promotes IFN-β production through a regulatory mechanism involving cross-talk between DNA and RNA sensor pathways, and our data support the hypothesis that bacterial RNA can drive a host immune response.