title: Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice.
abstract: Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. Adult BALB/c mice were intranasally exposed to low-dose house-dust-mite (or vehicle) daily for 10 days. On day 9, mice were inoculated with human-rhinovirus-1B (or UV-inactivated human-rhinovirus-1B). Forty-eight hours after inoculation, we assessed bronchoalveolar cellular inflammation, levels of relevant cytokines/serum antibodies, lung function and responsiveness/sensitivity to methacholine. House-dust-mite exposure did not result in a classical TH2-driven response, but was more representative of noneosinophilic asthma. However, there were significant effects of house-dust-mite exposure on most of the parameters measured including increased cellular inflammation (primarily macrophages and neutrophils), increased total IgE and house-dust-mite-specific IgG1 and increased responsiveness/sensitivity to methacholine. There were limited effects of human-rhinovirus-1B infection alone, and the combination of the two insults resulted in additive increases in neutrophil levels and lung parenchymal responses to methacholine (tissue elastance). We conclude that acute rhinovirus infection exacerbates house-dust-mite-induced lung disease in adult mice. The similarity of our results using the naturally occurring allergen house-dust-mite, to previous studies using ovalbumin, suggests that the exacerbation of allergic airways disease by rhinovirus infection could act via multiple or conserved mechanisms.
authors.affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, The University of Western Australia, Subiaco, Western Australia, Australia; Pharmacology, Pharmacy and Anaesthesiology Unit, School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Phan
authors.affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, The University of Western Australia, Subiaco, Western Australia, Australia; School of Paediatrics and Child Health, The University of Western Australia, Subiaco, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kicic
authors.affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, The University of Western Australia, Subiaco, Western Australia, Australia; School of Paediatrics and Child Health, The University of Western Australia, Subiaco, Western Australia, Australia.
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Berry
authors.affiliation: Pharmacology, Pharmacy and Anaesthesiology Unit, School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Lynette B
authors.initials: LB
authors.lastname: Fernandes
authors.affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, The University of Western Australia, Subiaco, Western Australia, Australia; School of Paediatrics and Child Health, The University of Western Australia, Subiaco, Western Australia, Australia.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Zosky
authors.affiliation: Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, The University of Western Australia, Subiaco, Western Australia, Australia; School of Paediatrics and Child Health, The University of Western Australia, Subiaco, Western Australia, Australia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Larcombe
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018893:Bronchoalveolar Lavage; D005260:Female; D006967:Hypersensitivity / Q000276:immunology; D018793:Interleukin-13 / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D009297:Nasal Mucosa / Q000821:virology; D039981:Pyroglyphidae / Q000276:immunology*; D012129:Respiratory Function Tests; D012229:Rhinovirus / Q000276:immunology / Q000502:physiology*
chemical_list: D000914:Antibodies, Viral; D018793:Interleukin-13; D016210:Methacholine Chloride