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

A major risk factor for influenza infection is secondary bacterial pneumonia [31] . As β6 KO mice were protected from individual influenza and S. pneumoniae challenges, we tested the β6 KO mice with a secondary bacterial challenge model. Mice were inoculated intranasally with a sublethal dose of A/Puerto Rico/8/34 H1N1 influenza virus, and 7 dpi administered a low dose Inhibiting increased β6 integrin levels during respiratory infections is protective. β6 KO or WT mice were intranasally inoculated with CA/09 H1N1 influenza virus (10 4 TCID 50 ) and monitored for (A) β6 mRNA expression in lungs as quantitated by qPCR and normalized to GAPDH as a control. Data is pooled from 2 independent experiments with n = 2 mice per group. p< 0.0001 by Student's t test; (B) weight loss and (C) survival for 12 dpi. Data from (B) is pooled from 6 of S. pneumoniae (D39X strain) [32] . This dual infection model is generally lethal in WT mice, although neither challenge alone causes death [33] . Survival of WT mice after secondary challenge was~30%, while β6 KO mice were significantly protected (p = 0.0226) with 70% survival (Fig 1G) highlighting the importance of β6 integrin in the pathogenesis of respiratory infections.