Role of NK cells in influenza infection

Within days after infection, natural killer (NK) cells are recruited to the lungs and play an essential role in the immune response against influenza infection. Through interactions with the virus itself, as well as viral-infected cells, NK cells secrete a variety of cytokines and can contain viral replication by killing infected cells early after influenza infection. However, the virus has means of evading NK cell responses, including escaping NK cell recognition through mutation of the viral hemagglutinin (HA) protein, regulating HA levels, and by directly infecting and destroying NK cells. Although much of our understanding of NK cell role in influenza infection has come from animal models, there is increasing information from human infection. Studies conducted during the 2009 H1N1 pandemic provided much needed information on the importance of NK cells during human infection and suggest that NK lymphopenia may correlate with increased disease severity. However, more information on how different influenza virus subtypes influence NK cell levels and activities, the role of the different NK cell receptors in infection, and the impact of NK cells on human infection, particularly in high risk populations is needed.