Using the Mycobacterium marinum model system we found that infection with wild type bacilli (Mmar), but not with an isogenic ESX-1-deficient mutant (MmarΔRD1), induced significant release of mitochondrial and nuclear DNA into the macrophage cytosol (Fig 6B), and that M. marinum activated the type I IFN response in an ESX-1- and cGAS-dependent manner (Fig 6C). Here, ELF3 is linked to infection.