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

Christopher E Andoniou^1, 2, Serani L H van Dommelen^1, 2, 5, Valentina Voigt^1, 2, Daniel M Andrews^1, 2, Geraldine Brizard², Carine Asselin-Paturel³, Thomas Delale³, Katryn J Stacey⁴, Giorgio Trinchieri^4, 5 & Mariapia A Degli-Esposti^1, 2

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

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

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

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

⁵  Present addresses: Peter MacCallum Cancer Centre, East Melbourne 3002, Victoria, Australia (S.L.H.v.D.) and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA (G.T.).

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