A role for plasmacytoid dendritic cells in the rapid IL-18-dependent activation of NK cells following HSV-1 infection

Barr, DP; Belz, GT; Reading, PC; Wojtasiak, M; Whitney, PG; Heath, WR; Carbone, FR; Brooks, AG

Author(s): Barr, DP; Belz, GT; Reading, PC; Wojtasiak, M; Whitney, PG; Heath, WR; Carbone, FR; Brooks, AG;
Details: Publication Year 2007-05,Volume 37,Issue #5,Page 1334-1342
Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
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.
Publisher: WILEY-V C H VERLAG GMBH
Keywords: NATURAL-KILLER-CELLS; GAMMA-INDUCING FACTOR; IFN-GAMMA; INTERFERON-GAMMA; T-CELLS; DIFFERENTIAL REGULATION; GENE-EXPRESSION; CUTTING EDGE; IN-VIVO; IL-18
Publisher's Version: https://doi.org/10.1002/eji.200636362
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-05-01 12:00:00