Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224, USA.
Mech Ageing Dev. 2011 Oct;132(10):503-10. doi: 10.1016/j.mad.2011.08.005. Epub 2011 Aug 27.
Influenza is a public health concern, especially for the elderly. While influenza vaccination is efficacious in the young, it offers only limited protection in the elderly. Thus, it becomes imperative to understand age-related changes in the primary response to influenza infection. This study identified potential age-related defects in natural killer (NK) cell function during influenza infection. We showed that NK cells from aged mice were reduced and had impaired function and altered phenotype in lungs during influenza infection. Aged NK cells demonstrated decreased IFN-γ production, but not degranulation, after influenza infection. However, after ex vivo activation with YAC-1 cells, aged NK cells demonstrated both reduced IFN-γ production and degranulation. IFN-γ was also reduced in aged NK cells after activation with anti-NKp46 and soluble cytokines. IFN-β, and IL-12p40 mRNA expression was not significantly different from that observed in adult mice. Analysis of NK cell subsets indicated that aged mice had more immature and less terminally mature NK cells. These data suggest that aging affects the numbers, function and phenotype of NK cells. Thus, these defects in NK cell function could impair the ability of aged mice to induce a strong antiviral immune response during the early stages of the infection.
流感是一个公共卫生关注点，特别是对老年人而言。虽然流感疫苗在年轻人中有效，但对老年人的保护作用有限。因此，了解流感感染时与年龄相关的原发性反应变化至关重要。本研究确定了在流感感染期间自然杀伤 (NK) 细胞功能的潜在与年龄相关的缺陷。我们发现，流感感染期间，老年小鼠的 NK 细胞减少，功能受损，肺中的表型发生改变。感染流感后，老年 NK 细胞 IFN-γ 的产生减少，但脱颗粒没有减少。然而，用 YAC-1 细胞体外激活后，老年 NK 细胞 IFN-γ 的产生和脱颗粒均减少。用抗 NKp46 和可溶性细胞因子激活后，老年 NK 细胞中的 IFN-γ 也减少。IFN-β 和 IL-12p40 mRNA 的表达与成年小鼠观察到的没有显著差异。NK 细胞亚群分析表明，老年小鼠具有更多不成熟和较少终末成熟的 NK 细胞。这些数据表明，衰老会影响 NK 细胞的数量、功能和表型。因此，NK 细胞功能的这些缺陷可能会削弱老年小鼠在感染早期诱导强烈抗病毒免疫反应的能力。
