Maturation, activation, and protection of dendritic cells induced by double-stranded RNA.
The initiation of an immune response is critically dependent on the activation of dendritic cells (DCs). This process is triggered by surface receptors specific for inflammatory cytokines or for conserved patterns characteristic of infectious agents. Here we show that human DCs are activated by influenza virus infection and by double-stranded (ds)RNA. This activation results not only in increased antigen presentation and T cell stimulatory capacity, but also in resistance to the cytopathic effect of the virus, mediated by the production of type I interferon, and upregulation of MxA. Because dsRNA stimulates both maturation and resistance, DCs can serve as altruistic antigen-presenting cells capable of sustaining viral antigen production while acquiring the capacity to trigger naive T cells and drive polarized T helper cell type 1 responses.
Basel Institute for Immunology, CH-4005 Basel, Switzerland. cella@bii.ch
M
M
Cella
M
M
Salio
Y
Y
Sakakibara
H
H
Langen
I
I
Julkunen
A
A
Lanzavecchia
D017951:Antigen Presentation; D000998:Antiviral Agents / Q000096:biosynthesis; D019898:Autocrine Communication; D003588:Cytopathogenic Effect, Viral; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D019204:GTP-Binding Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D064547:Myxovirus Resistance Proteins; D009975:Orthomyxoviridae / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D014176:Protein Biosynthesis; D012330:RNA, Double-Stranded / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000998:Antiviral Agents; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D010455:Peptides; D012330:RNA, Double-Stranded; D019204:GTP-Binding Proteins