VACCINATION PROMOTES TH1-LIKE INFLAMMATION AND SURVIVAL IN CHRONIC PSEUDOMONAS-AERUGINOSA PNEUMONIA IN RATS

被引:39
作者
JOHANSEN, HK
HOUGEN, HP
CRYZ, SJ
RYGAARD, J
HOIBY, N
机构
[1] UNIV COPENHAGEN,BARTHOLIN INST,INST FORENS MED,COPENHAGEN,DENMARK
[2] UNIV COPENHAGEN,INST MED MICROBIOL & IMMUNOL,COPENHAGEN,DENMARK
[3] SWISS SERUM & VACCINE INST,CH-3001 BERN,SWITZERLAND
关键词
D O I
10.1164/ajrccm.152.4.7551392
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
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页码:1337 / 1346
页数:10
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