Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats.
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.
Johansen
H K
HK
Department of Clinical Microbiology, University Institute of Forensic Medicine, Bartholin Institute, Copenhagen, Denmark.
Hougen
H P
HP
Cryz
S J
SJ
Rygaard
J
J
Høiby
N
N
D000464:Alginates; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines; D003550:Cystic Fibrosis / Q000150:complications; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008168:Lung / Q000473:pathology; D009504:Neutrophils / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011552:Pseudomonas Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D014611:Vaccination
D000464:Alginates; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines