Prolonged cell survival may contribute to the cytokine storm observed during the coinfection of influenza A virus (IAV) and Streptococcus pneumoniae.

Abstract

Coinfection with influenza A virus (IAV) and Streptococcus pneumoniae is known to cause severe pneumonia. Numerous reports suggests an inappropriate immune response plays an important role in this disease. Many reports have examined signaling pathways responsible for the excessive immune response to coinfection, but the role for cell death in mediating inflammation during coinfection is not well understood. The inflammasome is a caspase-1 containing protein complex that activates interleukin-1β (IL-1β) and induces a pro-inflammatory form of cell death termed pyroptosis. We have discovered enhanced IL-1β levels during coinfection of macrophages with IAV and S. pneumoniae. Furthermore, inflammatory macrophages/monocytes, but not alveolar macrophages, are the major cell type producing IL-1β in the lung. However, this is not due to increased inflammasome activation. Intriguingly, coinfected macrophages are less prone to cell death than those singly infected with S. pneumoniae. Thus, we have elucidated a mechanism whereby prolonged cell survival may contribute to the cytokine storm observed during coinfection.