Influenza virus infection causes neutrophil dysfunction through reduced G-CSF production and an increased risk of secondary bacteria infection in the lung.

The immunological mechanisms of secondary bacterial infection followed by influenza virus infection were examined. When mice were intranasally infected with influenza virus A and then infected with P. aeruginosa at 4 days after viral infection, bacterial clearance in the lung significantly decreased compared to that of non-viral infected mice. Neutrophils from viral infected mice showed impaired digestion and/or killing of phagocytized bacteria due to reduced myeloperoxidase (MPO) activity. G-CSF production in the lungs of viral infected mice was lower than that of non-viral infected mice after secondary bacterial infection. When viral infected mice were injected with G-CSF before secondary bacterial infection, the MPO activity of viral infected mice restored to the same level as that of non-infected mice. Bacteria clearance in viral infected mice was also recovered by G-CSF administration. Thus, neutrophil dysfunction caused by influenza virus is attributed to insufficient G-CSF production, which induces a secondary bacterial infection.