Department of Animal Science, University of Florida, Gainesville, FL, USA.
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Sci Rep. 2016 Nov 29;6:37999. doi: 10.1038/srep37999.
Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses. We show that intranasal but not systemic administration of α-GalCer to piglets infected with pandemic A/California/04/2009 (CA04) H1N1 IAV ameliorated disease symptoms and resulted in the restoration of weight gain to the level of uninfected pigs. Correspondingly, viral titers in the upper-and lower-respiratory tract were reduced only in piglets that had received intranasal α-GalCer. Most significantly, lung inflammation as a consequence of virus persistence was largely prevented when NKT-cells were targeted via the respiratory route. Thus, targeting mucosal NKT-cells may provide a novel and potent platform for improving the course of disease in swine infected with seasonal and pandemic influenza viruses, and leads to the suggestion that this may also be true in humans and therefore deserves further study.
猪流感病毒（IAV）是导致猪和人类呼吸道疾病的主要原因。目前批准的抗流感疗法直接针对病毒，但随着新的病毒株迅速产生耐药性，这些方法的效果正在减弱。为了克服这一挑战，迫切需要更有效的抗病毒药物。在这里，我们测试了不变自然杀伤 T（NKT）细胞超级激动剂α-半乳糖神经酰胺（α-GalCer）的抗流感功效，它可刺激广泛的抗病毒免疫反应。我们发现，感染大流行性 A/加利福尼亚/04/2009（CA04）H1N1 IAV 的仔猪经鼻内而非全身给予α-GalCer 可改善疾病症状，并使体重恢复到未感染猪的水平。相应地，仅在接受鼻内α-GalCer 的仔猪中，上呼吸道和下呼吸道中的病毒滴度才降低。最重要的是，当通过呼吸道靶向 NKT 细胞时，可大大防止因病毒持续存在而引起的肺部炎症。因此，针对粘膜 NKT 细胞可能为改善感染季节性和大流行性流感病毒的猪的疾病进程提供一种新颖而有效的平台，并提示这在人类中也可能是正确的，因此值得进一步研究。
