Age‐associated changes and importance of Natural Killer cell functions during primary influenza infection in mice

The role of Natural Killer (NK) cells during the immune response to primary influenza infection in young and aged mice were investigated. Young (6∼8 weeks) and aged (22 months) C57BL/6 mice were infected intranasally with influenza A virus (H1N1, PR8) and NK cell‐mediated cytotoxicity was determined in lung and spleen during the first 4 days of infection. Aged mice demonstrated both a decrease in influenza‐inducible NK cytotoxicity and a reduction in the percentage and number of NK cells relative to young mice. While young mice exhibited a peak over a baseline on day 2 post infection (p.i.) with a statistical significance, such an increase was not observed in aged mice. Young mice also exhibited 2‐fold increase in perforin and granzyme at day 2 p.i. coinciding with a peak of NK cytotoxicity activity. In order to further establish the importance of NK cells in controlling influenza infection, NK cells were depleted in young mice using anti‐NK1.1 antibody prior to infection. Young mice depleted of NK cells exhibited increased weight loss and lung virus titer during early course of infection compared to young or aged mice. These data indicate that NK cells function is impaired in response to primary influenza infection in aged mice. More importantly, these results underscore the essential role of NK cells in controlling virus titers in lung, at the site of infection, during the early course of influenza infection, regardless of age.