NK cells require type I IFN receptor for antiviral responses during genital HSV-2 infection

Type I interferon (IFN) signalling, NM cells and NK cell-derived IFN-gamma are critical in the early control of genital HSV-2 infection. We have recently reported that NM cells are the source of early IFN-gamma 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 NM cells compared to wild type controls. There was no detectable IFN-gamma production in the genital washes from IFN-alpha/beta R(-/-) 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 NM cells to the genital mucosa. Moreover, the absence of IL-12 had no significant effect on NM cell-derived IFN-gamma. Surprisingly, IFN-alpha/beta R(-/-) 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 NM cells. There was no significant differences in the levels of IL-15 receptor expression on NM cells from IFN-alpha/beta R(-/-) 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. (C) 2011 Elsevier Inc. All rights reserved.