title: 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-alpha/beta), 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-alpha/beta 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-alpha/beta in the ability to stimulate expression of maturation markers and chemokines by human monocyte-derived DC, with IFN-omega being the most unique in its effects. Pre-treatment with IFN-alpha/beta 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-alpha/beta 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-alpha/beta and TLR ligands simultaneously. Taken together, these results indicate a complex role for IFN-alpha/beta in regulating DC function during the course an infection, which varies according to IFN-alpha/beta subtype and the timing of exposure to other stimuli.
authors.affiliation: The Edward Jenner Institute for Vaccine Research, Compton, Newbury, UK.
authors.forename: Josef
authors.initials: J
authors.lastname: Walker
authors.forename: David F
authors.initials: DF
authors.lastname: Tough
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007370:Interferon Type I / Q000145:classification / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000502:physiology
chemical_list: D007370:Interferon Type I; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4