Influenza A viruses (IAV) are a major cause of respiratory diseases in pigs. Invariant natural killer T (iNKT) cells are an innate-like T cell subset that contribute significantly to IAV resistance in mice. In the current work, we explored whether expanding and activating iNKT cells with the iNKT cell superagonist α-galactosylceramide (α-GalCer) would change the course of an IAV infection in pigs. In one study, α-GalCer was administered to pigs intramuscularly (i.m.) 9 days before infection, which systemically expanded iNKT cells. In another study, α-GalCer was administered intranasally (i.n.) 2 days before virus infection to activate mucosal iNKT cells. Despite a synergistic increase in iNKT cells when α-GalCer i.m. treated pigs were infected with IAV, neither approach reduced disease signs, lung pathology, or virus replication. Our results indicate that prophylactic use of iNKT cell agonists to prevent IAV infection is ineffective in pigs. This is significant because this type of approach has been considered for humans whose iNKT cell levels and IAV infections are more similar to those of pigs than mice.

甲型流感病毒 (IAV) 是导致猪呼吸道疾病的主要原因。不变的自然杀伤 T (iNKT) 细胞是一种先天样 T 细胞亚群，对小鼠的 IAV 抗性有显着贡献。在目前的工作中，我们探讨了用 iNKT 细胞超激动剂 α-半乳糖神经酰胺 (α-GalCer) 扩增和激活 iNKT 细胞是否会改变猪 IAV 感染的过程。在一项研究中，在感染前 9 天给猪肌肉注射 (im) α-GalCer，从而系统性地扩增了 iNKT 细胞。在另一项研究中，在病毒感染前 2 天鼻内（in）给予 α-GalCer 以激活粘膜 iNKT 细胞。尽管当用 IAV 感染 α-GalCer im 处理的猪时 iNKT 细胞协同增加，但两种方法都不能减少疾病体征、肺部病理学或病毒复制。我们的结果表明，预防性使用 iNKT 细胞激动剂来预防 IAV 感染对猪无效。这很重要，因为这种方法已被考虑用于 iNKT 细胞水平和 IAV 感染与猪而非小鼠更相似的人类。