Interleukin 15-dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation.
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.
Kuwajima
Seiichi
S
Department of Immunology, Akita University School of Medicine, Akita 010-8543, Japan.
Sato
Taku
T
Ishida
Kazuto
K
Tada
Hiroyuki
H
Tezuka
Hiroyuki
H
Ohteki
Toshiaki
T
D000818:Animals; D020296:Animals, Congenic; D039521:CD11c Antigen / Q000235:genetics / Q000502:physiology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured / Q000276:immunology; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D019409:Interleukin-15 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011828:Radiation Chimera; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D039521:CD11c Antigen; D019013:CD40 Antigens; D019409:Interleukin-15; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma