title: Plasmacytoid dendritic cells limit viral replication, pulmonary inflammation, and airway hyperresponsiveness in respiratory syncytial virus infection.
abstract: Plasmacytoid dendritic cells (pDC), as major producers of IFN-alpha, are thought not only to be pivotal in antiviral immunity, but also to limit allergic inflammation. In this study, we delineate the role of pDC in a mouse model of respiratory syncytial virus (RSV)-induced airway inflammation. Bone marrow-derived pDC generated high levels of IFN-alpha upon RSV infection, and the percentage of pDC expressing MHC class II and maturation-associated costimulatory molecules was increased. However, their weak Ag-presenting capacity was not enhanced. Furthermore, pDC induced marked levels of IL-10 in T cell cultures irrespective of infection. In vivo, numbers of pDC in the lung increased early after RSV infection and remained elevated throughout the inflammatory phase and the resolution phase of infection. Depletion of pDC resulted in increases in peak RSV titers, pulmonary inflammation, and airway hyperresponsiveness. In contrast, adoptive transfer of activated pDC to the airways reduced RSV copy numbers. In conclusion, RSV infection induces activation of murine pDC with robust IFN-alpha production, limiting replication and accelerating elimination of RSV. In addition to this innate response, pDC also may play an immune regulatory role in reducing pulmonary inflammation and inhibiting the development of airway hyperresponsiveness.
authors.affiliation: Department of Respiratory Medicine, National Heart and Lung Institute and Wright Fleming Institute of Infection and Immunity, Imperial College London, London W2 1PG, United Kingdom.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Nina
authors.initials: N
authors.lastname: Peters
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schwarze
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000032:analysis; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D051379:Mice; D011024:Pneumonia, Viral / Q000276:immunology* / Q000473:pathology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D018113:Respiratory Syncytial Virus, Human / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
chemical_list: D039521:CD11c Antigen; D016898:Interferon-alpha