title: Respiratory syncytial virus-induced exaggeration of allergic airway disease is dependent upon CCR1-associated immune responses.
abstract: Severe respiratory syncytial virus (RSV) infection has a significant impact on airway function, and may alter subsequent development of asthma. CCR1 mRNA was significantly up-regulated during primary RSV infection in BALB/c mice, and was also up-regulated during allergen exposure in sensitized mice. Although CCR1(-/-) mice exhibited similar levels of airway hyperresponsiveness (AHR) as wild-type mice in response to cockroach allergen alone, in animals treated with RSV prior to cockroach antigen (CRA) sensitization and challenge, a significant decrease in exacerbated AHR was observed in the CCR1(-/-) mice. The reduction in AHR after RSV and allergen challenge in CCR1(-/-) mice was not associated with changes in peribronchial eosinophilia, but was accompanied by significantly decreased IL-13 levels in the lungs, as well as an absence of mucus cell staining within the airways. When T lymphocyte numbers were compared in animals receiving CRA to animals receiving a combination of RSV and allergen an increase in both CD4 and CD8 T lymphocytes could be detected in wild-type but not CCR1(-/-) animals. Thus, these data suggest that CCR1-mediated responses have a primary role for inducing severe disease during RSV infection, and may be responsible for altering the lung pathophysiological responses to subsequent allergen challenges via IL-13-mediated mechanisms.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
authors.forename: Alison E
authors.initials: AE
authors.lastname: John
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Gerard
authors.forename: Matthew
authors.initials: M
authors.lastname: Schaller
authors.forename: Allison L
authors.initials: AL
authors.lastname: Miller
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Berlin
authors.forename: Allison A
authors.initials: AA
authors.lastname: Humbles
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology; D003058:Cockroaches / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D018793:Interleukin-13 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009093:Mucus / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation
chemical_list: D000485:Allergens; C515300:CCR1 protein, human; C515301:Ccr1 protein, mouse; D018793:Interleukin-13; D012333:RNA, Messenger; D054389:Receptors, CCR1; D019707:Receptors, Chemokine