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


METHODS
C57BL/6 mice were randomly inoculated with PA-laden agarose beads (1 × 10(5) CFU/50 μL) or planktonic PA (1 × 10(5) CFU/50 μL), 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-β1, IFN-γ, IL-1β, IL-4, IL-6, IL-10, and IL-17A were measured. Messenger RNA (mRNA) levels of TGF-β1, 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-β1 and higher concentrations of IFN-γ, IL-1β, IL-6, and IL-17A in BAL fluid. Meanwhile, they had significantly lower mRNA levels of TGF-β1, 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.
1Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University , Shanghai , China.
Feng-Ming
FM
Ding
Song-Lei
SL
Zhu
Ce
C
Shen
Xiao-Li
XL
Ji
Xin
X
Zhou
D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa; D011897:Random Allocation; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10
Pseudomonas aeruginosa; chronic lung infection; cytokine; regulatory T cell; transcription factor