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

Nat Immunol. 2005 Oct;6(10):1011-9. doi: 10.1038/ni1244. Epub 2005 Sep 4.


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-alpha and interactions between the NKG2D activating receptor and NKG2D ligand, whereas the production of interferon-gamma 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-alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11 Antigens / biosynthesis
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Herpesviridae Infections / immunology*
  • Interferon-alpha / biosynthesis
  • Interferon-gamma / biosynthesis
  • Interleukin-18
  • Killer Cells, Natural / immunology*
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Muromegalovirus / immunology*
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell


  • CD11 Antigens
  • Interferon-alpha
  • Interleukin-18
  • Klrk1 protein, mouse
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Interferon-gamma