An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens

Meliopoulos, Victoria A.; Van de Velde, Lee-Ann; Van de Velde, Nicholas C.; Karlsson, Erik A.; Neale, Geoff; Vogel, Peter; Guy, Cliff; Sharma, Shalini; Duan, Susu; Surman, Sherri L.; Jones, Bart G.; Johnson, Michael D. L.; Bosio, Catharine; Jolly, Lisa; Jenkins, R. Gisli; Hurwitz, Julia L.; Rosch, Jason W.; Sheppard, Dean; Thomas, Paul G.; Murray, Peter J.; Schultz-Cherry, Stacey

To determine if type I IFN signaling was also increased in epithelial cells, primary bronchotracheal epithelial cells (mTEC) from WT and β6 KO mice were isolated, differentiated and grown at the air-liquid interface prior to infection with CA/09 virus (MOI 0.1). Phosphorylated and total levels of STAT1 and IRF3 were quantitated at 24 hours post-infection by immunoblot (Fig 8H) . β6 KO mTEC exhibited significant increases in total STAT1 and IRF3 levels as compared to WT mTEC after infection as well as at baseline, although differences in phosphorylated STAT1 and IRF3 were minimal (Fig 8H and S6E Fig) . Based on these data, we concluded that regulation of type I IFNs was dysregulated in the lungs of β6 KO mice at baseline, and that hematopoietic cells as well as epithelial cells may be involved.