Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats.

Abstract

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.

Interferon-gamma (IFN-γ) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

“…We did not observe any effect of IFN-on the antibody-mediated response after 2 weeks [19,29]. This is not surprising, however, since in the 'natural course' of chronic P. aeruginosa lung infection in rats, IgM antibodies peak 1 week after challenge [18], whereas the IgG and IgA antibody responses reach highest levels from 4 to 13 weeks after challenge [18]. Furthermore, administration of IFN-after challenge resulted in a significant decrease in macroscopic pathology changes compared with rats stimulated before challenge and controls.…”

“…Seven-week old female Lewis rats (Charles River, Würtzburg, Germany) weighing 160-180 g were used for this study [18].…”

Dendritic Cells Stimulated withActinobacillus actinomycetemcomitansElicit Rapid Gamma Interferon Responses by Natural Killer Cells

“…This DC-dependent pathway may help to provide the IFN-␥ necessary for the high levels of IgG2 that are associated with less severe periodontal disease (5,6,25,44). However, it is also of some concern that the prolonged production of Th1 cytokines in sites of chronic inflammation has been associated with tissue damage (1,4,9,17,35,38). Thus, the DC-driven immune response to A. actinomycetemcomitans could help to induce adaptive immune responses that might have destructive as well as protective effects.…”

“…These results prompted the hypothesis that the initial host-pathogen interface established between A. actinomycetemcomitans and immature DCs might enhance IFN-␥ production, which in turn might promote immunopathology as well as protective IgG2 expression (1,4,9,17,22,35,38,39). To begin testing, we compared the levels of IL-12 production by mDCs and macrophages stimulated with Escherichia coli and A. actinomycetemcomitans.…”

Enhanced Immunogenicity in the Murine Airway Mucosa with an AttenuatedSalmonellaLive Vaccine Expressing OprF-OprI fromPseudomonas aeruginosa

“…A TH1 phenotype was reported to relate to a better clinical outcome in a cross-sectional clinical study (28). Several animal studies demonstrated a better outcome of P. aeruginosa lung infection by interventions that initiate a shift towards a TH1-type response (20,26,27). It remains to be determined in experimental and clinical studies whether the enhanced airway immunogenicity of the present OprF-OprI live vaccine approach would translate into a better protection against P. aeruginosa.…”