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

Nature Immunology volume 7, pages 740–746 (2006)Cite this article

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.

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Figure 1: Impaired IL-12 and IFN-γ production in CpG-injected IL-15-deficient mice.
Figure 2: Essential function of DCs in CpG-induced IL-12 and IFN-γ production.
Figure 3: DC-derived IL-15 is critical for CpG-induced immune activation.
Figure 4: CpG-induced immune activation requires pDCs.
Figure 5: Mechanism of crosstalk between cDCs and pDCs.
Figure 6: Type I interferon is dispensable for CpG-induced immune activation.

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Acknowledgements

We thank M. Shibata, N. Kakizaki and K. Onodera for animal care; K. Yamashita and Y. Abe for experimental support; K. Hasegawa for discussions; S. Jung (Weizmann Institute of Science, Rehovot, Israel) for DTR-GFP mice; T.W. Mak (Campbell Family Institute, Toronto, Canada) for B6 Il2rb−/− mice; H. Kikutani (Osaka University, Suita, Japan) for B6 Cd40−/− mice; R. Abe (Tokyo University of Science, Noda, Japan) for B6 Cd40lg−/− mice; and H. Yagita (Juntendo University, Tokyo, Japan) for mAb MR1. Supported by the Toray Science Foundation (T.O.), the Takeda Science Foundation (T.O.), the Novartis Foundation for the Promotion of Science (T.O.), the Sankyo Foundation for Life Science (T.O.), a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan (16017212 and 16043204 to T.O.), a Grant-in-Aid for Creative Scientific Research by the Japan Society for the Promotion of Science (13GS0015) and the Japan Society for the Promotion of Science for Young Scientists (H.T.).

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  1. Department of Immunology, Akita University School of Medicine, Akita, 010-8543, Japan

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

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Supplementary information

Supplementary Fig. 1

The kinetic analysis of serum IFN-γ production after CpG injection. (PDF 250 kb)

Supplementary Fig. 2

The kinetic analysis of serum IL-12 p70 production after CpG injection. (PDF 247 kb)

Supplementary Figure 3

A system of mixed BM-chimeras. (PDF 520 kb)

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Kuwajima, S., Sato, T., Ishida, K. et al. Interleukin 15–dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation. Nat Immunol 7, 740–746 (2006). https://doi.org/10.1038/ni1348

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