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Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity

Nature Immunology volume 6, pages 1011–1019 (2005)Cite this article

Abstract

Dendritic cells (DCs) regulate various aspects of innate immunity, including natural killer (NK) cell function. Here we define the mechanisms involved in DC–NK cell interactions during viral infection. NK cells were efficiently activated by murine cytomegalovirus (MCMV)–infected CD11b+ DCs. NK cell cytotoxicity required interferon-α and interactions between the NKG2D activating receptor and NKG2D ligand, whereas the production of interferon-γ by NK cells relied mainly on DC-derived interleukin 18. Although Toll-like receptor 9 contributes to antiviral immunity, we found that signaling pathways independent of Toll-like receptor 9 were important in generating immune responses to MCMV, including the production of interferon-α and the induction of NK cell cytotoxicity. Notably, adoptive transfer of MCMV-activated CD11b+ DCs resulted in improved control of MCMV infection, indicating that these cells participate in controlling viral replication in vivo.

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Figure 1: CD11b+ DCs produce cytokines in response to MCMV.
Figure 2: CD11b+ DCs infected with MCMV activate NK cells.
Figure 3: DC-derived type I interferons are required for the activation of NK cell cytotoxicity.
Figure 4: IFN-γ production by NK cells is dependent on DC-derived IL-12 and IL-18.
Figure 5: Ligation of NKG2D in DC–NK cell cocultures contributes to the activation NK cell cytotoxicity.
Figure 6: Transfer of MCMV-activated CD11b+ DCs reduces MCMV replication in vivo.
Figure 7: The IFN-α response to MCMV is dependent on TLR9 in pDCs but not in CD11b+ DCs.
Figure 8: TLR9 deficiency does not affect NK cell cytotoxicity, and its effect on MCMV replication is organ specific.

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Acknowledgements

We thank S. Akira (Research Institute for Microbial Diseases, Osaka University, Osaka, Japan) for generating and providing mice deficient in IL-18, MyD88, TLR2, TLR4 and TLR9; R. Flavell (Yale University School of Medicine, New Haven, Connecticut) for generating and providing mice deficient in TLR3; M. Smyth (Peter MacCallum Cancer Centre, Melbourne, Australia) for advice and for providing mice deficient in IL-12, IL-18 and both IL-12 and IL18; and H. Tabarias and J. Dunn for technical assistance. Supported by the National Health and Medical Research Council of Australia and by a Wellcome Trust Overseas Senior Research Fellowship in Biomedical Science in Australia (M.A.D.-E.).

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Author notes

  1. Serani L H van Dommelen

    Present address: Peter MacCallum Cancer Centre, East Melbourne, 3002, Victoria, Australia

  2. Giorgio Trinchieri

    Present address: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

Authors and Affiliations

  1. Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Crowley, 6009, Western Australia, Australia

    Christopher E Andoniou, Serani L H van Dommelen, Valentina Voigt, Daniel M Andrews & Mariapia A Degli-Esposti

  2. Centre for Experimental Immunology, Lions Eye Institute, Nedlands, 6009, Western Australia, Australia

    Christopher E Andoniou, Serani L H van Dommelen, Valentina Voigt, Daniel M Andrews, Geraldine Brizard & Mariapia A Degli-Esposti

  3. Schering-Plough Laboratory for Immunological Research, Dardilly, 69571, France

    Carine Asselin-Paturel & Thomas Delale

  4. Institute for Molecular Bioscience, Cooperative Research Centre for Chronic Inflammatory Diseases, University of Queensland, Brisbane, 4072, Australia

    Katryn J Stacey & Giorgio Trinchieri

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Correspondence to Mariapia A Degli-Esposti.

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Supplementary information

Supplementary Fig. 1

MCMV infection of CD11b+DCs induces NKG2DL expression. (PDF 58 kb)

Supplementary Fig. 2

Production of IL-12 by CD11b+DCs requires TLR9-mediated signals. (PDF 64 kb)

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Andoniou, C., van Dommelen, S., Voigt, V. et al. Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity. Nat Immunol 6, 1011–1019 (2005). https://doi.org/10.1038/ni1244

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