Natural killer cell function is altered during the primary response of aged mice to influenza infection

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.