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Nature Immunology 7, 740–746 (1 July 2006) | doi:10.1038/ni1348

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

Seiichi Kuwajima , Taku Sato , Kazuto Ishida , Hiroyuki Tada , Hiroyuki Tezuka & Toshiaki Ohteki

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.