title: Respiratory syncytial virus infection modifies and accelerates pulmonary disease via DC activation and migration.
abstract: In the present studies, we have established that RSV can elicit a more pathogenic environment dependent on improper DC-associated sensitization. Our initial studies demonstrated that RSV, but not influenza, infection during an allergen exposure into the airway induced a more severe allergen response. The RSV-induced exacerbation included an increased Th2 cytokine response and pathophysiology as monitored by AHR and mucus overproduction. DCs played a central role in the allergen-induced responses, as instilling RSV-infected BMDC into the airway could recapitulate a live virus challenge. With the use of CCR6-/- mice that have a primary defect in the recruitment of mDC subsets, reduced exacerbation of disease was observed when RSV was administered along with allergen. Furthermore, sensitization of mice with RSV-infected BMDC into the airway produced a more severe immune response to a live virus challenge. Subsequently, using RSV-infected BMDC from CCR7-/- mice (that do not migrate efficiently to LNs) to sensitize the exacerbated response demonstrated that the response was dependent on DC migration to the LN. Finally, the ability of RSV-infected DCs to elicit an exacerbated, allergen-induced pathogenic response could be maintained for as long as 3 weeks, suggesting that RSV-infected DCs themselves created an altered immune environment that impacts off-target mucosal responses that could have prolonged effects.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Sihyug
authors.initials: S
authors.lastname: Jang
authors.forename: Joost
authors.initials: J
authors.lastname: Smit
authors.forename: Lara E
authors.initials: LE
authors.lastname: Kallal
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054399:Receptors, CCR6 / Q000502:physiology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*
chemical_list: D000485:Allergens; C498126:CCR6 protein, mouse; D054399:Receptors, CCR6
keywords: T cells; cytokines; immune responses