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