title: A critical role for IL-15 in TLR-mediated innate antiviral immunity against genital HSV-2 infection.
abstract: 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.
authors.affiliation: Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Thatte
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: DeWitte-Orr
authors.forename: Brian
authors.initials: B
authors.lastname: Lichty
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mossman
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006558:Herpes Genitalis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007372:Interferons / Q000096:biosynthesis; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051193:Toll-Like Receptors / Q000378:metabolism*; D014709:Vero Cells
chemical_list: C525069:CpG phosphorothioate ODN 1826-S; D019409:Interleukin-15; D008024:Ligands; D051193:Toll-Like Receptors; D004247:DNA; D007372:Interferons