Respiratory syncytial virus decreases the capacity of myeloid dendritic cells to induce interferon-gamma in naïve T cells.
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants under 6 months of age. Since an RSV infection does not necessarily prevent a reinfection, we asked whether RSV might subvert an effective immune response by interfering with the function of dendritic cells (DCs). Immature DCs cultured from cord blood stem cells and infected with RSV reduced the rate of interferon-gamma (IFN-gamma) production in co-cultured autologous naïve T cells stimulated with the superantigen TSST-1. Maturation of DCs in response to poly(IC) but not to CD40 ligand did overcome the inhibitory effect of RSV. Further experiments demonstrated that induction of apoptosis, a selective increase in CD86 expression and lack of release of pro-inflammatory cytokines were associated with inhibition of IFN-gamma generation. In addition, RSV replication seemed to be essential for modulation of IFN-gamma production because a virus preparation inactivated by UV irradiation had no effect. Hence, one reason for multiple reinfections by RSV might be the subversion of antiviral immune responses by interference of RSV with DC function.
Bartz
H
H
Klinik für Kinder und Jugendmedizin der Ruhr Universität Bochum im St. Josef Hospital, Alexandrinenstr. 5, Germany.
Türkel
O
O
Hoffjan
S
S
Rothoeft
T
T
Gonschorek
A
A
Schauer
U
U
D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D051940:B7-2 Antigen; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D008562:Membrane Glycoproteins; D007371:Interferon-gamma