Type I interferon signaling in hematopoietic cells impairs neutrophil antibacterial function in the middle ear during viral co-infection.

The most common infection of childhood is otitis media, caused by bacterial infection of the middle ear. In children with otitis media, middle ear inflammation corresponds with acute infection and greater viral pathogen carriage. In mice, induction of a type I interferon (IFN) response is sufficient to increase Streptococcus pneumoniae middle ear infection. In contrast to the mechanisms of virus-induced immune dysfunction described in the lungs, the critical cellular targets of type I IFN are irradiation-sensitive cells, namely, myeloid cells. Type I IFN receptor (IFNAR) signaling impairs neutrophil phagocytic capacity, corresponding with reduced S. pneumoniae clearance from the middle ear. Middle ear neutrophils from children with otitis media also demonstrate impaired phagocytosis. Last, type I IFN-driven neutrophil extracellular traps (NETs) reduce the number of functional neutrophils in mouse and human samples. These findings highlight neutrophil function as a key target of virus-associated immune dysregulation during otitis media.