Interleukin 15-dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation

Nat Immunol. 2006 Jul;7(7):740-6. doi: 10.1038/ni1348. Epub 2006 May 21.

Abstract

The function of interleukin 15 (IL-15) in unmethylated CpG oligodeoxynucleotide (CpG)-induced immune responses remains unknown. Here, in response to CpG, both wild-type and natural killer cell-depleted mice produced IL-12 and became resistant to a lethal dose of Listeria monocytogenes. In contrast, CpG-treated IL-15-deficient mice produced little IL-12 and succumbed to L. monocytogenes. CpG-stimulated conventional dendritic cells (cDCs) were the main producers of both IL-15 and IL-12, but cDCs did not produce IL-12 in the absence of plasmacytoid DCs (pDCs). The cDC-derived IL-15 induced CD40 expression by cDCs. Interaction between CD40 on cDCs and CD40 ligand on pDCs led to IL-12 production by cDCs. Thus, IL-15-dependent crosstalk between cDCs and pDCs is essential for CpG-induced immune activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Congenic
  • CD11c Antigen / genetics
  • CD11c Antigen / physiology
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology
  • CD40 Ligand / genetics
  • CD40 Ligand / immunology
  • Cell Communication
  • Cells, Cultured / immunology
  • CpG Islands / genetics
  • CpG Islands / immunology*
  • Dendritic Cells / classification
  • Dendritic Cells / immunology
  • Dendritic Cells / physiology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunologic Memory
  • Interferon-gamma / physiology
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / genetics
  • Interleukin-15 / biosynthesis
  • Interleukin-15 / deficiency
  • Interleukin-15 / genetics
  • Interleukin-15 / physiology*
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Radiation Chimera
  • Recombinant Fusion Proteins / physiology
  • T-Lymphocyte Subsets / immunology

Substances

  • CD11c Antigen
  • CD40 Antigens
  • Interleukin-15
  • Recombinant Fusion Proteins
  • CD40 Ligand
  • Interleukin-12
  • Interferon-gamma