title: Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media.
abstract: Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus). We and others have demonstrated that coinfection with IAV facilitates the replication of pneumococci in the middle ear. Specifically, we 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 trap (NET) formation in the middle ear, which, instead of clearing the infection, allows 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 novel insight into how pneumococci are able to replicate in the middle ear cavity and induce disease.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Australia.
authors.forename: Kirsty R
authors.initials: KR
authors.lastname: Short
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
authors.forename: Jeroen D
authors.initials: JD
authors.lastname: Langereis
authors.forename: Keng Yih
authors.initials: KY
authors.lastname: Chew
authors.forename: Emma R
authors.initials: ER
authors.lastname: Job
authors.forename: Charles W
authors.initials: CW
authors.lastname: Armitage
authors.forename: Brandon
authors.initials: B
authors.lastname: Hatcher
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hermans
authors.forename: Odilia L
authors.initials: OL
authors.lastname: Wijburg
authors.forename: Dimitri A
authors.initials: DA
authors.lastname: Diavatopoulos
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000502:physiology*; D000914:Antibodies, Viral / Q000502:physiology*; D058491:Bacterial Load; D060085:Coinfection / Q000382:microbiology* / Q000821:virology; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000382:microbiology; D006801:Humans; D009980:Influenza A virus / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000382:microbiology; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral