The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/3/821/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 5, March 1, 1999 821-829

Articles

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

Marina Cella*, Mariolina Salio*, Yoichi Sakakibara*, Hanno Langen{ddagger}, Ilkka Julkunen§, and Antonio Lanzavecchia*

From the * Basel Institute for Immunology, CH-4005 Basel, Switzerland; {ddagger} 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.

Key Words: dendritic cell maturation and activation • influenza virus • double-stranded RNA • type I interferon • MxA

Address correspondence to Marina Cella or Antonio Lanzavecchia, Basel Institute for Immunology, Grenzacherstrasse 487, CH 4005 Basel, Switzerland. Phone: 41-61-6051326; Fax: 41-61-6051222; E-mail: cella{at}bii.ch or lanzavecchia{at}bii.ch

M. Salio holds an EC fellowship (EUNIDI). The Basel Institute for Immunology was founded and is supported by Hoffmann-La Roche, Basel, Switzerland.

Abbreviations used: CD40L, CD40 ligand; DC, dendritic cell; ds, double-stranded; MOI, multiplicity of infection.


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