A Protective Role of Interleukin-15 in a Mouse Model for Systemic Infection with Herpes Simplex Virus

Abstract

To define the role of cytokine binding to the IL-2/IL-15Rβ chain in protective immunity against systemic infection with herpes simplex virus type 2 (HSV-2), IL-2/IL-15 receptor(R)β knock-out mice were inoculated intraperitoneally with HSV-2 strain 186. IL-2/IL-15Rβ-deficient mice were susceptible to systemic HSV-2 infection compared with their heterozygous littermates. The emergence of natural killer (NK) cells was impaired in IL-2/IL-15Rβ knock-out mice, but CD4+ T cell receptor (TCR) αβ+ T cells were normally detected in the peritoneal cavity after infection with HSV-2. However, the generation of HSV-2-specific CD4+ T helper (Th) 1 cells producing interferon-γ was impaired in IL-2/IL-15Rβ knock-out mice following HSV-2 infection. The serum IL-15 level in control mice was increased in the early stage after HSV-2 infection but was not detectable in IL-2/IL-15Rβ knock-out mice. In vivo administration of recombinant IL-15 protected normal mice from HSV-2-induced lethality, accompanied by increases in numbers of NK cells and HSV-2-specific Th1 cells. Taken together, these results suggest that IL-15, using the IL-2/IL15Rβ chain, plays an important role in mounting protective immunity during the course of systemic HSV-2 infection.