Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
, 127 (2), 206-13

Improved Outcome of Chronic Pseudomonas Aeruginosa Lung Infection Is Associated With Induction of a Th1-dominated Cytokine Response

Affiliations
Comparative Study

Improved Outcome of Chronic Pseudomonas Aeruginosa Lung Infection Is Associated With Induction of a Th1-dominated Cytokine Response

C Moser et al. Clin Exp Immunol.

Abstract

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.

Figures

Fig. 1
Fig. 1
Cumulative survival of BALB/c mice after (—) single or (—) re-infection with alginate-embedded Pseudomonas aeruginosa in the lungs. Significantly more singly-infected BALB/c mice died than re-infected mice (P < 0·005). Event times (○) re-infected, (□) single.
Fig. 2
Fig. 2
Total number of cells in the lungs. Numbers of nucleated cells were determined after staining with crystal violet. Significantly increased numbers of cells after infection with alginate-embedded Pseudomonas aeruginosa were observed in the BALF (P ≤ 0·02). Νο differences in cell numbers between the groups were observed in the lung tissue. (○) BALB/c non-infected (n = 5 (4 BAL)); (□) BALB/c re-infected (n = 6); (▵) BALB/c singly-infected (n = 5 (4 BAL)).
Fig. 3
Fig. 3
The number of CD4 cells in the lungs of singly-infected, re-infected or non-infected BALB/c mice. Re-infected mice had significantly of CD4 cells in the lungs compared with non-infected mice (tissue: P < 0·02 and BAL: P ≤ 0·01). In addition, singly-infected mice had increased numbers of CD4 cells in BALF (P < 0·05). No significant differences were observed between the singly- and re-infected groups. (○) BALB/c non-infected (n = 5 (4 BAL)); (□) BALB/c re-infected (n = 6); (▵) BALB/c singly-infected (n = 5 (4 BAL)).
Fig. 4
Fig. 4
Surface expression of LFA-1 on CD4 cells in the lungs as analysed by FACS and presented as mean fluorescence intensity. An increase in LFA-1 surface expression on CD4+ cells from infected mice was observed both in tissue and BALF (P < 0·03). Moreover, an increase in LFA-1 surface expression on CD4+ cells from lung tissue was observed after re-infection as compared with single infection (P < 0·3). (○) BALB/c non-infected (n = 5 (4 BAL)); (□) BALB/c re-infected (n = 6); BALB/c singly-infected (n = 5 (4 BAL)).
Fig. 5
Fig. 5
The ratio between pulmonary IL-4 and IFN-γ release from mice singly- or re-infected with Pseudomonas aeruginosa lung infection. Lungs were enzymatically-digested and the isolated cells were stimulated for 6 h with anti-CD3. The cytokine concentration was determined by ELISA. The ratio decreased significantly on re-infection of BALB/c mice (P < 0·007). (□) BALB/c re-infected (n = 6); BALB/c singly-infected (n = 5).
Fig. 6
Fig. 6
(a) Pulmonary IFN-γ release from mice singly- or re-infected with Pseudomonas aeruginosa in the lungs. Lungs were enzymatically-digested and the isolated cells were stimulated for 48h with P. aeruginosa OMP. The cytokine concentration was determined by ELISA. Both singly- and re-infected mice had significantly increased IFN-γ levels compared with non-infected mice (P < 0·01). However, re-infected mice had increased IFN-γ levels compared with singly-infected mice (P < 0·01). (b) Pulmonary IL-12 release from mice singly- or re-infected with P. aeruginosa in the lungs. Isolated cells from enzymatically-digested lungs were stimulated with P. aeruginosa OMP for 48 h. The cytokine concentration was determined by ELISA. Re-infected mice had significantly increased IL-12 levels compared with non-infected mice (P < 0·02) and singly-infected mice (P < 0·03). (○) BALB/c non-infected (n = 5); (□) BALB/c re-infected (n = 6); (▵) BALB/c singly-infected (n = 5).
Fig. 6
Fig. 6
(a) Pulmonary IFN-γ release from mice singly- or re-infected with Pseudomonas aeruginosa in the lungs. Lungs were enzymatically-digested and the isolated cells were stimulated for 48h with P. aeruginosa OMP. The cytokine concentration was determined by ELISA. Both singly- and re-infected mice had significantly increased IFN-γ levels compared with non-infected mice (P < 0·01). However, re-infected mice had increased IFN-γ levels compared with singly-infected mice (P < 0·01). (b) Pulmonary IL-12 release from mice singly- or re-infected with P. aeruginosa in the lungs. Isolated cells from enzymatically-digested lungs were stimulated with P. aeruginosa OMP for 48 h. The cytokine concentration was determined by ELISA. Re-infected mice had significantly increased IL-12 levels compared with non-infected mice (P < 0·02) and singly-infected mice (P < 0·03). (○) BALB/c non-infected (n = 5); (□) BALB/c re-infected (n = 6); (▵) BALB/c singly-infected (n = 5).

Similar articles

See all similar articles

Cited by 29 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback