Activation of invariant NKT cells enhances the innate immune response and improves the disease course in influenza A virus infection
Activation of invariant NKT cells enhances the innate immune response and improves the disease course in influenza A virus infection
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DOI：
10.1002/eji.200738017
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发表时间：
2008-07-01
影响因子：
5.4
通讯作者：
McMichael, Andrew J.
中科院分区：
文献类型：
--
作者：
Ho, Ling-Pei;Denney, Laura;McMichael, Andrew J.
不变NKT（iNKT）细胞在抗病毒免疫中具有不容置疑的作用，尽管这些细胞发挥其功能的机制尚未完全阐明。随着高致病性甲型流感病毒感染在人类中的重要性日益显现，我们质疑iNKT细胞是否有助于针对甲型流感病毒的免疫防御，以及这些细胞的激活是否会影响结果。我们发现，在流感病毒感染期间，用α-半乳糖神经酰胺（α-GC）激活iNKT细胞短暂增强了早期先天免疫应答，而不影响T细胞免疫，并降低了C57 BL/6小鼠肺中的早期病毒滴度。这是伴随着一个更好的疾病过程与改善体重减轻概况。肝脏、血液和肺中iNKT细胞的时间变化表明，在给予α-GC的小鼠中，iNKT细胞从肝脏活化并迁移至肺。病毒滴度的改善似乎依赖于通过腹膜内途径激活iNKT细胞，因为鼻内施用α-GC没有相同的效果。我们的结论是，iNKT细胞的激活增强了肺部的早期先天免疫反应，有助于抗病毒免疫和改善甲型流感病毒感染的病程。
Invariant NKT (iNKT) cells have an indubitable role in antiviral immunity, although the mechanisms by which these cells exert their functions are not fully elucidated. With the emerging importance of high-pathogenicity influenza A virus infections in humans, we questioned whether iNKT cells contribute to immune defence against influenza A virus and whether activation of these cells influences outcome. We show that activation of iNKT cells with a-galactosylceramide (alpha-GC) during influenza virus infection transiently enhanced early innate immune response without affecting T cell immunity, and reduced early viral titres in lungs of C57BL/6 mice. This is accompanied by a better disease course with improved weight loss profile. Temporal changes in iNKT cells in the liver, blood and lungs suggest activation and migration of iNKT cells from the liver to the lungs in mice that were administered alpha-GC. improvement in viral titres appears dependent on activation of iNKT cells via the intraperitoneal route since intranasal administration of alpha-GC did not have the same effect. We conclude that activation of iNKT cells enhances early innate immune response in the lungs and contribute to antiviral immunity and improved disease course in influenza A virus infection.