Modification of TLR-induced activation of human dendritic cells by type I IFN: Synergistic interaction with TLR4 but not TLR3 agonists

Abstract

Upon detection of direct and indirect signs of infection, dendritic cells (DC) undergo functional changes that modify their ability to elicit immune responses. Type I interferon (IFN-α/β), which includes a large family of closely related infection-inducible cytokines, represents one indirect signal that can act as a DC stimulus. We have investigated the ability of IFN-α/β subtypes to affect DC function and to influence DC responses to Toll-like receptor (TLR) agonists (i.e., direct infection-associated signals). Subtle differences were observed among 15 subtypes of IFN-α/β in the ability to stimulate expression of maturation markers and chemokines by human monocyte-derived DC, with IFN-ω being the most unique in its effects. Pre-treatment with IFN-α/ β did not alter the ability of DC to mature in response to subsequent contact with TLR agonists, but did modulate their secretion of chemokines. Conversely, IFN-α/β was shown to act synergistically with TLR4 but not TLR3 agonists for the induction of maturation and chemokine production when DC were exposed to IFN-α/β and TLR ligands simultaneously. Taken together, these results indicate a complex role for IFN-α/β in regulating DC function during the course an infection, which varies according to IFN-α/β subtype and the timing of exposure to other stimuli. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.