A critical role for IL-15 in TLR-mediated innate antiviral immunity against genital HSV-2 infection

Immunol Cell Biol. 2011 Aug;89(6):663-9. doi: 10.1038/icb.2011.7. Epub 2011 Feb 22.


Innate antiviral immunity, particularly at mucosal surfaces, has a critical role in early control of viral infections. Both type I interferons (IFNs) and interleukin-15 (IL-15) are essential components of innate antiviral immunity. It has been shown that toll-like receptor (TLR) ligand-induced innate antiviral immunity requires IFN-α/β and -λ receptor signaling. However, it is not known if IL-15 has a role in TLR ligand-mediated antiviral responses. Here, we report that ligands for TLR-3 and TLR-9 cannot confer protection against genital herpes simplex virus-2 (HSV-2) in the absence of IL-15 in vivo. Interestingly, wild-type mice depleted of natural killer (NK) cells and treated with TLR ligands are protected upon HSV-2 challenge, suggesting that the critical role of IL-15 is independent of NK cell-mediated activity. To examine the cytokine response in the absence of IL-15, we investigated TLR ligand-induced IFN-β and -λ production in the vaginal washes, but found no impairment in IL-15(-/-) mice. Finally, we report no impairment in the expression of the IFN-stimulated genes in IL-15(-/-) mice. Collectively, the data suggest that TLR ligands induce an IFN-mediated response in the vaginal tract of both wild-type and IL-15(-/-) mice, but its induction is insufficient for providing protection against HSV-2 in the absence of IL-15.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • DNA / immunology
  • Disease Models, Animal
  • Female
  • Herpes Genitalis / genetics
  • Herpes Genitalis / immunology*
  • Herpes Genitalis / prevention & control
  • Herpesvirus 2, Human / immunology*
  • Immunity, Innate*
  • Immunity, Mucosal
  • Interferons / biosynthesis
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism
  • Interleukin-15 / physiology*
  • Killer Cells, Natural / immunology
  • Ligands
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Toll-Like Receptors / metabolism*
  • Vero Cells


  • CpG phosphorothioate ODN 1826-S
  • Interleukin-15
  • Ligands
  • Toll-Like Receptors
  • DNA
  • Interferons