title: Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic cells to produce Th2 mediators through synergistic induction of IFN-{gamma} and Th1 chemokine production.
abstract: Depending on the activation status, plasmacytoid dendritic cells (PDC) and myeloid DC have the ability to induce CD4 T cell development toward T helper cell type 1 (Th1) or Th2 pathways. Thus, we tested whether different activation signals could also have an impact on the profile of chemokines produced by human PDC. Signals that induce human PDC to promote a type 1 response (i.e., viruses) and a type 2 response [i.e., CD40 ligand (CD40L)] also induced PDC isolated from tonsils to secrete chemokines preferentially attracting Th1 cells [such as interferon-gamma (IFN-gamma)-inducible protein (IP)-10/CXC chemokine ligand 10 (CXCL10) and macrophage inflammatory protein-1beta/CC chemokine ligand 4 (CCL4)] or Th2 cells (such as thymus and activation-regulated chemokine/CCL17 and monocyte-derived chemokine/CCL22), respectively. Activated natural killer cells were preferentially recruited by supernatants of virus-activated PDC, and supernatants of CD40L-activated PDC attracted memory CD4(+) T cells, particularly the CD4(+)CD45RO(+)CD25(+) T cells described for their regulatory activities. It is striking that CD40L and virus synergized to trigger the production of IFN-gamma by PDC, which induces another Th1-attracting chemokine monokine-induced by IFN-gamma/CXCL9 and cooperates with endogenous type I IFN for IP-10/CXCL10 production. In conclusion, our studies reveal that PDC participate in the selective recruitment of effector cells of innate and adaptive immune responses and that virus converts the CD40L-induced Th2 chemokine patterns of PDC into a potent Th1 mediator profile through an autocrine loop of IFN-gamma.
authors.affiliation: Laboratory for Immunological Research, Schering-Plough Research Institute, Dardilly, France. bendris@lyon.fnclcc.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bendriss-Vermare
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Burg
authors.forename: Holger
authors.initials: H
authors.lastname: Kanzler
authors.forename: Laurence
authors.initials: L
authors.lastname: Chaperot
authors.forename: Thomas
authors.initials: T
authors.lastname: Duhen
authors.forename: Odette
authors.initials: O
authors.lastname: de Bouteiller
authors.forename: Marjorie
authors.initials: M
authors.lastname: D'agostini
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bridon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durand
authors.forename: Joel M
authors.initials: JM
authors.lastname: Sederstrom
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Joël
authors.initials: J
authors.lastname: Plumas
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Jacob
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Pierre
authors.initials: P
authors.lastname: Garrone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.forename: Francine
authors.initials: F
authors.lastname: Brière
mesh_terms: D019898:Autocrine Communication / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology / Q000494:pharmacology*; D054370:Chemokine CXCL9; D018925:Chemokines / Q000096:biosynthesis* / Q000276:immunology; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology* / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000821:virology; D009975:Orthomyxoviridae / Q000276:immunology; D011994:Recombinant Proteins; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology
chemical_list: C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D007377:Interleukin-3; D011994:Recombinant Proteins; D023201:CD40 Ligand; D007371:Interferon-gamma