Since IL-27 signaling modulated influenza host defense, we investigated the role of IL-27 in viral, bacterial co-infection by challenging C57BL/6 and IL-27Rα−/− mice with influenza A/PR/8/34 H1N1 or vehicle (PBS) for 6 days followed by S. aureus (ATTC 49775) or vehicle (PBS). The gene discussed is IL27RA; the disease is influenza.