title: Influenza A facilitates sensitization to house dust mite in infant mice leading to an asthma phenotype in adulthood.
abstract: The origins of allergic asthma, particularly in infancy, remain obscure. Respiratory viral infections and allergen sensitization in early life have been associated with asthma in young children. However, a causal link has not been established. We investigated whether an influenza A infection in early life alters immune responses to house dust mite (HDM) and promotes an asthmatic phenotype later in life. Neonatal (8-day-old) mice were infected with influenza virus and 7 days later, exposed to HDM for 3 weeks. Unlike adults, neonatal mice exposed to HDM exhibited negligible immune responsiveness to HDM, but not to influenza A. HDM responsiveness in adults was associated with distinct Ly6c+ CD11b+ inflammatory dendritic cell and CD8α+ plasmacytoid (pDC) populations that were absent in HDM-exposed infant mice, suggesting an important role in HDM-mediated inflammation. Remarkably, HDM hyporesponsiveness was overcome when exposure occurred concurrently with an acute influenza infection; young mice now displayed robust allergen-specific immunity, allergic inflammation, and lung remodeling. Remodeling persisted into early adulthood, even after prolonged discontinuation of allergen exposure and was associated with marked impairment of lung function. Our data demonstrate that allergen exposure coincident with acute viral infection in early life subverts constitutive allergen hyporesponsiveness and imprints an asthmatic phenotype in adulthood.
authors: Division of Respiratory Diseases and Allergy, Center for Gene Therapeutics and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: A
authors: A
authors: Al-Garawi
authors: R
authors: R
authors: Fattouh
authors: F
authors: F
authors: Botelho
authors: T D
authors: TD
authors: Walker
authors: S
authors: S
authors: Goncharova
authors: C-L
authors: CL
authors: Moore
authors: M
authors: M
authors: Mori
authors: J S
authors: JS
authors: Erjefalt
authors: D K
authors: DK
authors: Chu
authors: A A
authors: AA
authors: Humbles
authors: R
authors: R
authors: Kolbeck
authors: M R
authors: MR
authors: Stampfli
authors: P M
authors: PM
authors: O'Byrne
authors: A J
authors: AJ
authors: Coyle
authors: M
authors: M
authors: Jordana
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D002454:Cell Differentiation; D060085:Coinfection / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D006801:Humans; D007114:Immunization; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D039981:Pyroglyphidae; D012129:Respiratory Function Tests
chemical_list: D015703:Antigens, CD; D039741:Antigens, Dermatophagoides