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2004 OMIG, Thygeson Lecture

OMIG Main Page | 2004 Abstracts

Pseudomonas aeruginosa: Models and Treatment of the Disease
Linda D. Hazlett, Ph.D.

Purpose: Pseudomonas aeruginosa is a common organism associated with bacterial keratitis, especially in extended wear contact lens users. Advances in our understanding of host innate and adaptive immune responses to experimental infection have been made using inbred murine models that are classed as resistant (cornea heals) vs. susceptible (cornea perforates).
Methods: A variety of immunological, microbiological, molecular and statistical analyses and approaches were used.
Results: Data provide evidence that sustained IL-12 driven IFN-γ production in dominant Th1 responder mouse strains such as C57BL/6 (B6) contributes to corneal destruction and perforation, while IL-18 driven production of IFN-γ (by NK cells) in the absence of IL-12 p40, is associated with bacterial killing and less corneal destruction in dominant Th2 responder strains such as BALB/c. Data also suggest that IFN-γ contributes to bacterial killing indirectly by regulating macrophage nitric oxide levels in cornea. The critical role of PMN in the innate response to bacterial infection will be discussed, as mice of either strain depleted of PMN and then infected, die within 48 hours. Regulation of PMN will be discussed and evidence from antibody neutralization experiments provided to show that persistence of PMN in B6 cornea is regulated by CD4+ T cells, while macrophages (and NK cells) regulate PMN number in the cornea of BALB/c mice. The importance of IL-1 and its neutralization or inhibition (caspase-1 inhibitor) will be discussed as a novel adjunctive treatment for bacterial keratitis.
Conclusions: These studies continue to provide better understanding of the inflammatory mechanisms that are operative in the cornea after P. aeruginosa challenge and are consistent with our long-term goals of providing targets for alternative or adjunctive treatment for this disease.

No commercial relationships. Grant support: NIH R01EY02986 and P30EY04068.

Disclosure code: N

OMIG Main Page | 2004 Abstracts

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