Novel Protective Mechanism for Interleukin-33 at the Mucosal Barrier during Influenza-associated Bacterial Super-infection

Influenza A is a highly contagious respiratory virus that causes seasonal epidemics and occasional worldwide pandemics. The primary cause of influenza-related mortality is bacterial super-infection. There are numerous mechanisms by which preceding influenza infection attenuates host defense, allowing for increased susceptibility to bacterial pneumonia. Herein, we demonstrate that influenza inhibits Staphylococcus aureus-induced production of IL-33. Restoration of IL-33 during influenza A and MRSA super-infection enhanced bacterial clearance and improved mortality. ILC2s and alternatively activated macrophages are not required for IL-33 mediated protection during super-infection. We show that IL-33 treatment resulted in neutrophil recruitment to the lung, associated with improved bacterial clearance. These findings identify a novel role for IL-33 in anti-bacterial host defense at the mucosal barrier.