Figure 1.

The mechanisms of enhanced host susceptibility to secondary bacterial infection by type I IFNs. Airway epithelial cells and alveolar macrophages are cells of the innate immune system that are at the first line of defense against infection in the airspaces. The influenza virus activates pattern recognition receptors expressed by airway epithelial cells and macrophages and leads to the production of type I IFNs, which are crucial in combating the infection. However, type I IFNs also induce an immunosuppressive state in the resolution phase of infection that enhances host susceptibility to secondary bacterial infection. These mechanisms include: (1) inhibition of IL-17-producing γδ T cells, (2) Induces macrophage epigenetic modifications, (3) Induces or inhibits inflammasome activation in a context-dependent manner, (4) Inhibits neutrophil and monocyte infiltration. These mechanisms result in a lung environment ill equipped to fight an increasing bacterial burden.