Toll-Like Receptor-Independent Triggering of Dendritic Cell Maturation by Viruses

The ability of vaccination to empower natural immune defenses against viral infection is well illustrated by the worldwide eradication of smallpox and the partial elimination of polio after global vaccination efforts (74, 98).Unfortunately, these major successes have been infrequent, and diverse viruses continue to threaten our societies.The development of new vaccines, or the improvement of existing ones, is currently hindered by a limited knowledge of the intracellular mechanisms leading to the activation of antiviral adaptive immunity and of the viral elements responsible for its triggering upon infection.The use of the viral RNA analog poly(I:C), the discovery of the highly virus-responsive plasmacytoid dendritic cells (pDCs), and the identification of Toll-like receptors (TLRs) specific for viral elements have led to a greater understanding of the initiation of antiviral immunity.Nevertheless, there is little evidence to suggest that these elements are sufficient-or even necessary-for adaptive antiviral immune responses.A more comprehensive understanding of the mechanisms by which viruses trigger the development of adaptive immunity is therefore still needed.Recent work led to the identification of a novel pathway for the activation of conventional DCs (cDCs), the primary cells responsible for the generation of adaptive immunity.The triggering of this pathway leads to strong adaptive antiviral immunity in vivo even in the absence of TLR signaling.Here, we review the evidence for the identification and characterization of this pathway.Intracellular molecular candidates that may participate in this pathway are discussed, and a model for the triggering of DC maturation by viruses is presented.