title: NK cells require type I IFN receptor for antiviral responses during genital HSV-2 infection.
abstract: Type I interferon (IFN) signalling, NK cells and NK cell-derived IFN-γ are critical in the early control of genital HSV-2 infection. We have recently reported that NK cells are the source of early IFN-γ in the genital tract in response to HSV-2. However, the response of NK cells to genital HSV-2 infection is not well defined in the context of type I IFN signalling. Here we show that HSV-2 replication was significantly higher in mice deficient in the type I IFN receptor or NK cells compared to wild type controls. There was no detectable IFN-γ production in the genital washes from IFN-α/βR(-/-) mice or NK cell depleted mice in response to HSV-2 infection compared to control mice. Absence of the type I IFN receptor does not alter homing of NK cells to the genital mucosa. Moreover, the absence of IL-12 had no significant effect on NK cell-derived IFN-γ. Surprisingly, IFN-α/βR(-/-) mice had more IL-15 positive cells in the genital mucosa in response to HSV-2 infection compared to control mice. We then examined the expression of IL-15 receptors on NK cells. There was no significant differences in the levels of IL-15 receptor expression on NK cells from IFN-α/βR(-/-) or control mice. Our data clearly suggest that type I IFN receptor signalling is essential for NK cell activation in response to genital HSV-2 infection, and propose that NK cell activation by IL-15 may involve type I IFNs.
authors.affiliation: Center for Gene Therapeutics and Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Navkiran
authors.initials: N
authors.lastname: Gill
authors.forename: Meghan J
authors.initials: MJ
authors.lastname: Chenoweth
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdu
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000503:physiopathology; D018258:Herpesvirus 2, Human; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D019409:Interleukin-15; D053633:Receptor, Interferon alpha-beta