However, recent studies reveal that IRFs critically drive nonviral infections through IFN-independent mechanisms, exemplified by IRF8 coordinating pan-autophagic gene expression to clear Listeria monocytogenes (11) and IRF1 suppressing autophagy to potentiate apoptosis in endotoxin-challenged macrophages (15), establishing IRFs as master regulators of infection-associated macrophage autophagy. The gene discussed is IRF8; the disease is infection.