Integration of ER stress and viral nucleotide sensing in DCs: mounting a response commensurate to the threat?

In response to inflammatory stimulation, DCs have a remarkable pattern of differentiation, including the triggering of specific mechanisms to control the immune response. In this issue of the European Journal of Immunology, a study reports that concomitant stimulation of pattern-recognition receptors by viral-type nucleic acids and induction of the unfolded protein response by chemicals synergize in DCs to augment type I interferon and pro-inflammatory cytokine production. Expression of the transcription factor XBP1 was shown to be necessary and sufficient to induce this synergistic effect. These findings confirm the existence of important connections between the unfolding protein response/ER stress pathway and the production of inflammatory cytokines, which have been recently revealed in different models and immune contexts, as discussed in this Commentary.