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Effector mechanisms of protection against Pseudomonas aeruginosa keratitis in immunized rats

journal contribution
posted on 06.12.2017, 00:00 by A Thakur, Jennelle KydJennelle Kyd, M Xue, M Willcox, A Cripps
Pseudomonas aeruginosa is an opportunistic pathogen which causes sight-threatening corneal infections in humans. The purpose of this study was to evaluate various immunization routes that may provide protection against Pseudomonas keratitis and to define the molecular mechanisms involved in the protection. Sprague-Dawley rats (10 to 12 weeks old) were immunized using paraformaldehyde-killed P. aeruginosa (strain 6206) via oral, nasal, and intra-Peyer’s patch (IPP) routes followed by an ocular topical booster dose. Scratched corneas were challenged with an infective dose of P. aeruginosa. Following clinical examination, eyes were enucleated for histology, polymorphonuclear leukocyte (PMN) quantitation, bacterial count, enzyme-linked immunosorbent assay, and RNase protection assay. PMN infiltration was higher early (4 h) during the infection in immunizedrats than in nonimmunized rats. Later during the infection, the number of PMNs diminished in immunized rats while in nonimmunized animals the number of PMNs continued to increase. Bacteria were cleared much faster from immunized groups than from the nonimmunized group, and the nasally immunized group had the most efficacious response among the immunized groups. Nasal and IPP immunization groups had increased cytokine expression of interleukin-2 (IL-2) and IL-5 and differed from each other for IL-6. All three immunizedgroups had significantly reduced IL-1b levels when compared with the nonimmunized rats and a significantly altered profile for CINC-1 expression. This study has shown that the route of immunization modulates the inflammatory response to ocular P. aeruginosa infection, thus affecting the severity of keratitis and adversepathology, with nasal immunization being the most effective.

Funding

Category 1 - Australian Competitive Grants (this includes ARC, NHMRC)

History

Volume

69

Issue

5

Start Page

3295

End Page

3304

Number of Pages

10

eISSN

1070-6313

ISSN

0019-9567

Location

United States

Publisher

American Society for Microbiology

Language

en-aus

Peer Reviewed

Yes

Open Access

No

External Author Affiliations

University of Canberra; University of New South Wales;

Era Eligible

No

Journal

Infection and immunity.

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