title: Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity.
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-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.
authors.affiliation: Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Crowley 6009, Western Australia, Australia.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Andoniou
authors.forename: Serani L H
authors.initials: SL
authors.lastname: van Dommelen
authors.forename: Valentina
authors.initials: V
authors.lastname: Voigt
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Andrews
authors.forename: Geraldine
authors.initials: G
authors.lastname: Brizard
authors.forename: Carine
authors.initials: C
authors.lastname: Asselin-Paturel
authors.forename: Thomas
authors.initials: T
authors.lastname: Delale
authors.forename: Katryn J
authors.initials: KJ
authors.lastname: Stacey
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Mariapia A
authors.initials: MA
authors.lastname: Degli-Esposti
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell
chemical_list: D018845:CD11 Antigens; D016898:Interferon-alpha; D020382:Interleukin-18; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma