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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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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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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DOI: https://doi.org/10.1038/ni1244
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