title: Influenza A virus facilitates Streptococcus pneumoniae transmission and disease.
abstract: Streptococcus pneumoniae (the pneumococcus) kills approximately 1.6 million people annually. Pneumococcal infections predominantly manifest as pneumonia, sepsis, meningitis, and otitis media. S. pneumoniae is also a member of the normal nasopharyngeal flora, colonizing up to 80% of children. Infection with influenza A virus (IAV) has been associated with both pneumococcal disease and transmission. However, to date no animal model has been available to investigate the role of IAV in the spread of S. pneumoniae. Here we investigate pneumococcal-influenza synergism with a particular focus on the role of IAV on pneumococcal transmission. Infant mice were colonized with S. pneumoniae and subsequently infected with IAV 3 d later. Using this novel model we show increased pneumococcal colonization and disease in the presence of IAV. Notably, in vivo imaging showed that IAV was essential for the transmission of S. pneumoniae from colonized ("index") mice to their naive cohoused littermates ("contacts"). Transmission occurred only when all mice were infected with IAV and was prevented when an IAV-neutralizing antibody was used to inhibit IAV replication in either index mice or contact mice. Together, these data provide novel insights into pneumococcal-influenza synergism and may indicate a previously unappreciated role of IAV in the spread of S. pneumoniae.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia. d.diavatopoulos@cukz.umcn.nl
authors.forename: Dimitri A
authors.initials: DA
authors.lastname: Diavatopoulos
authors.forename: Kirsty R
authors.initials: KR
authors.lastname: Short
authors.forename: John T
authors.initials: JT
authors.lastname: Price
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Wilksch
authors.forename: Lorena E
authors.initials: LE
authors.lastname: Brown
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.forename: Richard A
authors.initials: RA
authors.lastname: Strugnell
authors.forename: Odilia L
authors.initials: OL
authors.lastname: Wijburg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D009980:Influenza A virus / Q000502:physiology*; D007668:Kidney / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009305:Nasopharynx / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000635:transmission* / Q000821:virology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication