J. Exp. Med., Volume 189, Number 5, March 1, 1999 821-829

Maturation, Activation, and Protection of Dendritic Cells Induced by Double-stranded RNA

By Marina Cella,^* Mariolina Salio,^* Yoichi Sakakibara,^* Hanno Langen, Ilkka Julkunen,^§ and Antonio Lanzavecchia^*

From the ^* Basel Institute for Immunology, CH-4005 Basel, Switzerland;  Hoffmann-La Roche AG, CH-4002 Basel, Switzerland; and the ^§ National Public Health Institute, FIN-00300, Helsinki, Finland

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.

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• Wuthrich, M., Filutowicz, H. I., Warner, T., Deepe, G. S. Jr., Klein, B. S. (2003). Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement for CD4 Help in Exogenous Antigen Presentation to CD8+ T Cells: Implications for Vaccine Development in Immune-deficient Hosts. JEM 197: 1405-1416 [Abstract] [Full Text]  
• Santini, S.M., Di Pucchio, T., Lapenta, C., Parlato, S., Logozzi, M., Belardelli, F. (2003). A New Type I IFN-Mediated Pathway for the Rapid Differentiation of Monocytes into Highly Active Dendritic Cells. Stem Cells 21: 357-362 [Abstract] [Full Text]  
• Vieira, P. L., Heystek, H. C., Wormmeester, J., Wierenga, E. A., Kapsenberg, M. L. (2003). Glatiramer Acetate (Copolymer-1, Copaxone) Promotes Th2 Cell Development and Increased IL-10 Production Through Modulation of Dendritic Cells. J. Immunol. 170: 4483-4488 [Abstract] [Full Text]  
• Woltman, A. M., van Kooten, C. (2003). Functional modulation of dendritic cells to suppress adaptive immune responses. J. Leukoc. Biol. 73: 428-441 [Abstract] [Full Text]  
• Messmer, D., Messmer, B., Chiorazzi, N. (2003). The global transcriptional maturation program and stimuli-specific gene expression profiles of human myeloid dendritic cells. Int Immunol 15: 491-503 [Abstract] [Full Text]  
• Stober, D., Jomantaite, I., Schirmbeck, R., Reimann, J. (2003). NKT Cells Provide Help for Dendritic Cell-Dependent Priming of MHC Class I-Restricted CD8+ T Cells In Vivo. J. Immunol. 170: 2540-2548 [Abstract] [Full Text]  
• Sedlik, C., Orbach, D., Veron, P., Schweighoffer, E., Colucci, F., Gamberale, R., Ioan-Facsinay, A., Verbeek, S., Ricciardi-Castagnoli, P., Bonnerot, C., Tybulewicz, V. L. J., Di Santo, J., Amigorena, S. (2003). A Critical Role for Syk Protein Tyrosine Kinase in Fc Receptor-Mediated Antigen Presentation and Induction of Dendritic Cell Maturation. J. Immunol. 170: 846-852 [Abstract] [Full Text]  
• Qu, C., Moran, T. M., Randolph, G. J. (2003). Autocrine Type I IFN and Contact with Endothelium Promote the Presentation of Influenza A Virus by Monocyte-Derived APC. J. Immunol. 170: 1010-1018 [Abstract] [Full Text]  
• Kirman, J. R., Turon, T., Su, H., Li, A., Kraus, C., Polo, J. M., Belisle, J., Morris, S., Seder, R. A. (2003). Enhanced Immunogenicity to Mycobacterium tuberculosis by Vaccination with an Alphavirus Plasmid Replicon Expressing Antigen 85A. Infect. Immun. 71: 575-579 [Abstract] [Full Text]  
• Shi, L., Fatemi, S. H., Sidwell, R. W., Patterson, P. H. (2003). Maternal Influenza Infection Causes Marked Behavioral and Pharmacological Changes in the Offspring. J. Neurosci. 23: 297-302 [Abstract] [Full Text]  
• Ramirez, M. C., Sigal, L. J. (2002). Macrophages and Dendritic Cells Use the Cytosolic Pathway to Rapidly Cross-Present Antigen from Live, Vaccinia-Infected Cells. J. Immunol. 169: 6733-6742 [Abstract] [Full Text]  
• van der Kleij, D., Latz, E., Brouwers, J. F. H. M., Kruize, Y. C. M., Schmitz, M., Kurt-Jones, E. A., Espevik, T., de Jong, E. C., Kapsenberg, M. L., Golenbock, D. T., Tielens, A. G. M., Yazdanbakhsh, M. (2002). A Novel Host-Parasite Lipid Cross-talk. SCHISTOSOMAL LYSO-PHOSPHATIDYLSERINE ACTIVATES TOLL-LIKE RECEPTOR 2 AND AFFECTS IMMUNE POLARIZATION. J. Biol. Chem. 277: 48122-48129 [Abstract] [Full Text]  
• Krug, A., Uppaluri, R., Facchetti, F., Dorner, B. G., Sheehan, K. C. F., Schreiber, R. D., Cella, M., Colonna, M. (2002). Cutting Edge: IFN-Producing Cells Respond to CXCR3 Ligands in the Presence of CXCL12 and Secrete Inflammatory Chemokines upon Activation. J. Immunol. 169: 6079-6083 [Abstract] [Full Text]  
• Duperrier, K., Farre, A., Bienvenu, J., Bleyzac, N., Bernaud, J., Gebuhrer, L., Rigal, D., Eljaafari, A. (2002). Cyclosporin A inhibits dendritic cell maturation promoted by TNF-{alpha} or LPS but not by double-stranded RNA or CD40L. J. Leukoc. Biol. 72: 953-961 [Abstract] [Full Text]  

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