Respiratory viral infection can result in a temporary and nonspecific enhancement in resistance to subsequent respiratory infection. In the Proceedings of the National Academy of Sciences USA, Heaton and colleagues demonstrate that initial infection with influenza A virus renders mice more resistant to heterologous infection with influenza B virus. This resistance depends on club cells, a type of exocrine cell present in the respiratory epithelium. Club cells that survive infection show enhanced type I interferon signaling, and prior infection results in alterations in the transcription of genes encoding chemokines and proinflammatory cytokines in the lungs. Nonspecific resistance to infection with a second virus begins to diminish 6 weeks after the initial infection and is almost completely lost by 12 weeks, presumably due to natural turnover of the club cells. The precise mechanism used by club cells in this nonspecific resistance remains unclear.

Proc. Natl. Acad. Sci. USA (21 March 2016) doi:10.1073/pnas.1522376113