-Transgenic BALB/c Mice As a Model of Pseudomonas Aeruginosa Infections of the Cystic Fibrosis Lung

The opportunistic pathogen is responsible for much of the morbidity and mortality associated with cystic fibrosis (CF), a condition that predisposes patients to chronic lung infections. lung infections are difficult to treat because adapts to the CF lung, can develop multidrug resistance, and can form biofilms. Despite the clinical significance of , modeling infections in CF has been challenging. Here, we characterize -transgenic (Tg) BALB/c mice as lung infection models. -Tg mice overexpress the epithelial Na channel (ENaC) in their lungs, driving increased sodium absorption that causes lung pathology similar to CF. We intranasally infected -Tg mice and wild-type littermates with the laboratory strain PAO1 and CF clinical isolates and then assessed differences in bacterial clearance, cytokine responses, and histological features up to 12 days postinfection. -Tg mice carried higher bacterial burdens when infected with biofilm-grown rather than planktonic PAO1; -Tg mice also cleared infections more slowly than their wild-type littermates. Infection with PAO1 elicited significant increases in proinflammatory and Th17-linked cytokines on day 3. -Tg mice infected with nonmucoid early CF isolates maintained bacterial burdens and mounted immune responses similar to those of PAO1-infected -Tg mice. In contrast, -Tg mice infected with a mucoid CF isolate carried high bacterial burdens, produced significantly more interleukin 1β (IL-1β), IL-13, IL-17, IL-22, and KC, and showed severe immune cell infiltration into the bronchioles. Taken together, these results show the promise of -Tg mice as models of early colonization in the CF lung.