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.
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.
Bendriss-Vermare
Nathalie
N
Laboratory for Immunological Research, Schering-Plough Research Institute, Dardilly, France. bendris@lyon.fnclcc.fr
Burg
Stéphanie
S
Kanzler
Holger
H
Chaperot
Laurence
L
Duhen
Thomas
T
de Bouteiller
Odette
O
D'agostini
Marjorie
M
Bridon
Jean-Michel
JM
Durand
Isabelle
I
Sederstrom
Joel M
JM
Chen
Wei
W
Plumas
Joël
J
Jacob
Marie-Christine
MC
Liu
Yong-Jun
YJ
Garrone
Pierre
P
Trinchieri
Giorgio
G
Caux
Christophe
C
Brière
Francine
F
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
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