1. Respiratory syncytial virus infection modifies and accelerates pulmonary disease via DC activation and migration.
- Author
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Jang S, Smit J, Kallal LE, and Lukacs NW
- Subjects
- Animals, Female, Flow Cytometry, Lung Diseases pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Allergens immunology, Cell Movement immunology, Dendritic Cells immunology, Lung Diseases etiology, Receptors, CCR6 physiology, Respiratory Syncytial Virus Infections immunology, Respiratory Syncytial Viruses immunology
- 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.
- Published
- 2013
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