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.