| Title | RSV-induced dysregulation of expression of a mucosal beta-defensin augments colonization of the upper airway by nontypeable Haemophilus influenzae. | | Author(s) | McGillivary G, Mason KM, Jurcisek JA, Peeples ME, Bakaletz LO | | Institution | The Research Institute at Nationwide Children's Hospital, Center for Microbial Pathogenesis, The Ohio State University College of Medicine, Columbus, Ohio 43205. | | Source | Cell Microbiol 2009 Jun 2. | | Abstract | SUMMARY Otitis media (OM) is a polymicrobial disease wherein upper respiratory tract (URT) viruses compromise host airway defenses, 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 nontypeable Haemophilus influenzae (NTHI) from nasopharyngeal lavage fluids, compared to 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 URT. 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19500108 |
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