Although preceding influenza enhanced susceptibility to secondary S. aureus pneumonia in both WT and IL-27Rα−/− mice, the bacterial burden was significantly reduced in the co-infected IL-27Rα−/− mice compared to co-infected WT mice, suggesting that IL-27 signaling plays a role in the development of secondary S. aureus pneumonia in influenza, S. aureus co-infection. Here, IL27 is linked to influenza.