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 the enhanced survival seen in the β6 KO mice was associated with decreased ALI, we examined histological sections for evidence of tissue injury, alterations of the alveolar capillary barrier, and inflammatory responses [1] . Although groups were histologically similar at 3 dpi, at 7 dpi inflammation and thickened septa involving extensive areas of alveolar parenchyma was seen in WT lungs. In marked contrast, evidence of inflammation and tissue damage in the β6 KO lungs was generally limited to terminal bronchioles and small numbers of adjacent alveoli (Fig 2A) . Infected WT mice had increased TNF-α and IL-6 throughout the duration of infection, while the inflammatory cytokine response in β6 KO mice was less robust ( Fig 2B) . Evidence of alterations to the alveolar capillary barrier was found in infected WT mice beginning at 5 dpi as compared to KO mice (Fig 2C-2F ) including heavier lungs as determined by wet/dry weight ratios (5 dpi p = 0.0077, 7 dpi p = 0.0063) indicating increased edema ( Fig 2C) , accompanied by increased total protein (p < 0.0001, Fig 2D) and albumin in the bronchoalveolar lavage fluid (BALF) (7 dpi p < 0.0001, Fig 2E) and accumulation of Evans blue dye in the lungs of WT mice (p = 0.0071, Fig 2F) . Overall, β6 KO had decreased inflammation, acute lung injury, and improved survival during influenza infection.