Antibodies mediate the formation of neutrophil extracellular traps (NETs) in the middle ear and facilitate secondary pneumococcal otitis media.

Otitis media (OM; a middle ear infection) is a common childhood illness which can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a co-infection with as influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus). We and others have demonstrated that co-infection with IAV facilitates the replication of pneumococci in the middle ear. Specifically, we have used a mouse-model of OM to show that IAV facilitates the outgrowth of S. pneumoniae in the middle ear by inducing middle ear inflammation. Here, we seek to understand how the host inflammatory response facilitates bacterial outgrowth in the middle ear. Using B-cell deficient infant mice, we show that antibodies play a crucial role in facilitating pneumococcal replication. We subsequently show that this is due to antibody-dependent neutrophil extracellular traps (NETs) formation in the middle ear, which instead of clearing the infection allow the bacteria to replicate. We further demonstrate the importance of these NETs as a potential therapeutic target through the transtympanic administration of a DNase, which effectively reduces the bacterial load in the middle ear. Taken together, these data provide a novel insight into how pneumococci are able to replicate in the middle ear cavity and induce disease.