IL-15-dependent cross-talk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation

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Unmethylated CpG oligodeoxynucleotides （CpG） prevalent in bacteria and DNA viruses bind Toll-likereceptor（ TLR） 9 and directly stimulate DCs, thereby activating the innate and adaptive immune responses. CpG ispotentially a powerful reagent for protective immunity against infection by a wide variety of pathogens, for cancerand allergy therapies, and for the development of prophylactic and therapeutic vaccines. Here we investigated therole of interleukin （IL）-15 in the activation of CpG-induced immune responses. We show that upon CpG-priming,both wild-type（ WT） and NK cell-depleted WT mice produce interleukin（ IL）-12 p70 and become resistant to a lethaldose of Listeria monocytogenes（ LM）, whereas IL-15-/- mice impair IL-12 p70 production and succumb to the infection.Notably, CpG-stimulated conventional dendritic cells （cDCs） are the major producer of both IL-15 and IL-12 p70,but cDCs do not produce IL-12 in the absence of plasmacytoid DCs（ pDCs） in vivo. Importantly, cDC-derived IL-15induces CD40 expression on cDCs, which interacts with CD40 ligand on pDCs, leading to CD40 cross-linking and IL-12production. Collectively, these fi ndings show that IL-15-dependent cross-talk between cDCs and pDCs is essential forCpG-induced immune activation（ recently published in Nat Immunol 2006;7:740-6）