Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
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.
先天抗病毒免疫，特别是在黏膜表面，在早期控制病毒感染中起着关键作用。I 型干扰素（IFN）和白细胞介素-15（IL-15）是先天抗病毒免疫的重要组成部分。已经表明，Toll 样受体（TLR）配体诱导的先天抗病毒免疫需要 IFN-α/β 和 -λ 受体信号。然而，目前尚不清楚 IL-15 是否在 TLR 配体介导的抗病毒反应中发挥作用。在这里，我们报告说，TLR-3 和 TLR-9 的配体在体内缺乏 IL-15 的情况下不能提供对生殖器单纯疱疹病毒-2（HSV-2）的保护。有趣的是，耗尽自然杀伤（NK）细胞并用 TLR 配体处理的野生型小鼠在 HSV-2 攻击时受到保护，这表明 IL-15 的关键作用独立于 NK 细胞介导的活性。为了在缺乏 IL-15 的情况下检查细胞因子反应，我们研究了 TLR 配体诱导的阴道冲洗液中的 IFN-β 和 -λ 产生，但在 IL-15(-/-) 小鼠中未发现任何损伤。最后，我们报告说在 IL-15(-/-) 小鼠中没有发现 IFN 刺激基因的表达受损。总之，这些数据表明 TLR 配体在野生型和 IL-15(-/-) 小鼠的阴道中诱导 IFN 介导的反应，但在缺乏 IL-15 的情况下，其诱导不足以提供对 HSV-2 的保护。
