Regulatory T cell activity is partly inhibited in a mouse model of chronic Pseudomonas aeruginosa lung infection

Objectives: We aimed to investigate the activity of regulatory T (Treg) cells in chronic Pseudomonas aeruginosa (PA) lung infection and its influence on effector T-cell responses. Materials and Methods: C57BL/6 mice were randomly inoculated with PA-laden agarose beads (1 x 10(5) CFU/50 mu L) or planktonic PA (1 x 10(5) CFU/50 mu L), and euthanized at the time points of 4 hour, day 1, 3, 5, and 7. Bacterial load, bronchoalveolar lavage (BAL) fluid cell counts, and lung tissue histology were assessed. BAL fluid concentrations of TGF-beta 1, IFN-gamma, IL-1 beta, IL-4, IL-6, IL-10, and IL-17A were measured. Messenger RNA (mRNA) levels of TGF-beta 1, IL-10 and CD4(+) T-cell subtype-specific transcription factors were determined. The expression of CD4(+) CD25(+) forkhead box P3 (FoxP3)(+) cells in lungs and spleens were analyzed. Results: Mice inoculated with PA-laden agarose beads developed chronic PA lung infection during 7-day study period, while mice inoculated with planktonic PA cleared bacteria in 3 days. Compared with mice recovered from acute PA lung infection, those with chronic infection had significantly increased effector T-cell responses, accompanied by a more severe neutrophilic inflammation. Mice with chronic PA lung infection had significantly lower concentration of TGF-beta 1 and higher concentrations of IFN-gamma, IL-1 beta, IL-6, and IL-17A in BAL fluid. Meanwhile, they had significantly lower mRNA levels of TGF-beta 1, IL-10 and FoxP3 in lung tissues, and lower expression of CD4(+) CD25(+) FoxP3(+) cells in lungs and spleens. Conclusions: These findings indicate that Treg cell activity is partly inhibited in mice with chronic PA lung infection, which contributes to the enhanced effector T-cell responses in airways.