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

J Leukoc Biol. 2005 Oct;78(4):954-66. doi: 10.1189/jlb.0704383. Epub 2005 Aug 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autocrine Communication / immunology
  • CD40 Ligand / immunology
  • CD40 Ligand / pharmacology*
  • Chemokine CXCL9
  • Chemokines / biosynthesis*
  • Chemokines / immunology
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / immunology
  • Chemotaxis, Leukocyte / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / drug effects
  • Interferon-gamma / immunology*
  • Interferon-gamma / pharmacology
  • Interleukin-3 / pharmacology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / virology
  • Orthomyxoviridae / immunology
  • Recombinant Proteins
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th1 Cells / virology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Th2 Cells / virology

Substances

  • CXCL9 protein, human
  • Chemokine CXCL9
  • Chemokines
  • Chemokines, CXC
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-3
  • Recombinant Proteins
  • CD40 Ligand
  • Interferon-gamma