title: Influenza-induced inflammation drives pneumococcal otitis media.
abstract: Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.
authors: Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia. kirsty_short@yahoo.com
authors: Kirsty R
authors: KR
authors: Short
authors: Patrick C
authors: PC
authors: Reading
authors: Lorena E
authors: LE
authors: Brown
authors: John
authors: J
authors: Pedersen
authors: Brad
authors: B
authors: Gilbertson
authors: Emma R
authors: ER
authors: Job
authors: Kathryn M
authors: KM
authors: Edenborough
authors: Marrit N
authors: MN
authors: Habets
authors: Aldert
authors: A
authors: Zomer
authors: Peter W M
authors: PW
authors: Hermans
authors: Dimitri A
authors: DA
authors: Diavatopoulos
authors: Odilia L
authors: OL
authors: Wijburg
mesh_terms: D000818:Animals; D007249:Inflammation / Q000473:pathology*; D009980:Influenza A virus / Q000145:classification; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology / Q000382:microbiology / Q000821:virology; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D019562:Viral Load
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8