title: Respiratory syncytial virus-induced dysregulation of expression of a mucosal beta-defensin augments colonization of the upper airway by non-typeable Haemophilus influenzae.
abstract: Otitis media (OM) is a polymicrobial disease wherein upper respiratory tract viruses compromise host airway defences, which allows bacterial flora of the nasopharynx (NP) access to the middle ear. We have shown, in vitro, that respiratory syncytial virus (RSV), a viral co-pathogen of OM, reduces transcript abundance of the antimicrobial peptide (AP), chinchilla beta-defensin-1 (cBD-1). Here, we demonstrated that chinchillas inoculated with RSV expressed approximately 40% less cBD-1 mRNA and protein than did mock-challenged animals. Further, concurrent RSV infection resulted in a 10-100-fold greater recovery of non-typeable Haemophilus influenzae (NTHI) from nasopharyngeal lavage fluids, compared with chinchillas challenged with NTHI in the absence of viral co-infection. Additionally, when either: anti-cBD-1 antibody (to bind secreted AP) or recombinant cBD-1 (to increase AP concentration at the mucosal surface) were delivered to chinchillas, we demonstrated that disruption of the availability of a single AP influenced the relative load of NTHI in the upper respiratory tract. Collectively, our data suggested that effectors of innate immunity regulate normal bacterial colonization of the NP and, further, virus-induced altered expression of APs can result in an increased load of NTHI within the NP, which likely promotes development of OM.
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Center for Microbial Pathogenesis, The Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
authors.forename: Glen
authors.initials: G
authors.lastname: McGillivary
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Mason
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jurcisek
authors.forename: Mark E
authors.initials: ME
authors.lastname: Peeples
authors.forename: Lauren O
authors.initials: LO
authors.lastname: Bakaletz
mesh_terms: D000818:Animals; D002682:Chinchilla; D015169:Colony Count, Microbial; D020869:Gene Expression Profiling; D006192:Haemophilus Infections / Q000276:immunology* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000302:isolation & purification / Q000472:pathogenicity*; D009305:Nasopharynx / Q000382:microbiology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology; D023083:beta-Defensins / Q000096:biosynthesis* / Q000276:immunology*
chemical_list: D023083:beta-Defensins