Natural Killer Cells Recognize and Eliminate Influenza B via the Activating Receptor NKp46

Influenza virus infections annually result in worldwide health and economic burdens that affect the lives of millions. The most common type of influenza is influenza A. It evolves due to antigenic shifts and antigenic drifts and causes new pandemics every year. It is known that NK cells play an important role in the clearing of influenza A mostly through its natural cytotoxicity receptor, NKp46, binding to the viral protein hemagglutinin (HA).

All the research involving NK and influenza has been focused on influenza A, probably due to the fact that numerous different serotypes exist. However, little is known about the influenza B virus. Despite the fact that this type is only slowly evolving and only two different serotypes exist, influenza B still is responsible for third of all pediatric influenza deaths and is included in the seasonal vaccine each year.

In this research, we show that NKp46 also recognizes influenza B via binding to HA. We also demonstrate that the mechanism of binding and binding site are the same as in influenza A. Finally, we show that mice that do not express the NKp46 mouse orthologue, NCR1, show difficulties clearing the virus relative to WT mice.

In conclusion, the mechanism of recognition of HA by NKp46 enables the receptor to recognize both influenza A and influenza B in the same way. These findings emphasize the fact that NK cells are crucial in the immune response against influenza.