Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity.
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.
Andoniou
Christopher E
CE
Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Crowley 6009, Western Australia, Australia.
van Dommelen
Serani L H
SL
Voigt
Valentina
V
Andrews
Daniel M
DM
Brizard
Geraldine
G
Asselin-Paturel
Carine
C
Delale
Thomas
T
Stacey
Katryn J
KJ
Trinchieri
Giorgio
G
Degli-Esposti
Mariapia A
MA
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
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