title: A role for plasmacytoid dendritic cells in the rapid IL-18-dependent activation of NK cells following HSV-1 infection.
abstract: Natural killer (NK) cells play a crucial role in the initial response to viral infections but the mechanisms controlling their activation are unclear. We show a rapid and transient activation of NK cells that results in the production of IFN-gamma immediately following infection with herpes simplex virus type 1 (HSV-1). Activation of NK cells leading to synthesis of IFN-gamma was not mediated by a direct interaction with virus but required the presence of additional cell types and was largely dependent on the cytokine IL-18, but not IL-12. HSV-1-induced IFN-gamma expression by NK cells in vitro was impaired in spleen cultures depleted of CD11c(+) cells. Conversely, coculture of NK cells with virus-exposed conventional DC or plasmacytoid (p)DC restored the production of IFN-gamma, indicating that multiple DC subsets could mediate NK cell activation. While conventional DC populations stimulated NK cells independently of IL-18, they were less effective than pDC in promoting NK cell IFN-gamma expression. In contrast, the potent stimulation of NK cells by pDC was dependent on IL-18 as pDC from IL-18-deficient mice only activated a similar proportion of NK cells as conventional DC. These data identify IL-18 as a crucial factor for pDC-mediated NK cell regulation.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Australia.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Barr
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wojtasiak
authors.forename: Paul G
authors.initials: PG
authors.lastname: Whitney
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice
chemical_list: D020382:Interleukin-18; D007371:Interferon-gamma