Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats
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In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O-polysaccharide toxin A conjugate, or sterile saline. After challenge none of the rats immunized with D-ALG toxin A died, in contrast to the other two vaccine groups combined (p = 0.03). A significant reduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared with the other three groups (p = 0.009). The histopathologic response in the control rats was dominated by numerous polymorphonuclear leukocytes (PMN) surrounding the alginate beads. In contrast, the histopathologic response in rats immunized with D-ALG toxin A changed within the first week after challenge from predominantly PMNs (TH2-like) to a chronic-type inflammation dominated by mononuclear leukocytes (TH1-like). In accordance, the antibody titers induced by the D-ALG toxin A vaccine were not different from those of the control rats after challenge. This study identifies a possible new way of modifying the inflammation and thereby preventing the PMN-mediated lung tissue damage during chronic P. aeruginosa lung infection in CF.
Original language | English |
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Journal | American Journal of Respiratory and Critical Care Medicine |
Volume | 152 |
Issue number | 4 Pt 1 |
Pages (from-to) | 1337-46 |
Number of pages | 10 |
ISSN | 1073-449X |
Publication status | Published - 1995 |
- Alginates, Animals, Antibodies, Bacterial, Bacterial Vaccines, Cystic Fibrosis, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Leukocytes, Mononuclear, Lung, Neutrophils, Pneumonia, Bacterial, Pseudomonas Infections, Pseudomonas aeruginosa, Rats, Rats, Inbred Lew, Vaccination
Research areas
ID: 44354644