Corneal response to Pseudomonas aeruginosa infection.
Pseudomonas aeruginosa (P. aeruginosa) is a common organism associated with bacterial keratitis, especially in those who use extended wear contact lenses. Recent advances in our understanding of host innate and adaptive immune responses to experimental infection have been made using a variety of animal models, including inbred murine models that are classed as resistant (cornea heals) vs. susceptible (cornea perforates). Evidence has been provided that sustained IL-12-driven IFN-gamma production in dominant Th1 responder strains such as C57BL/6 (B6) contributes to corneal destruction and perforation, while IL-18-driven production of IFN-gamma in the absence of IL-12 is associated with bacterial killing and less corneal destruction in dominant Th2 responder strains such as BALB/c. The critical role of IL-1 and chemotactic cytokines such as MIP-2 in PMN recruitment and the critical role of this cell in the innate immune response to bacterial infection is reviewed. Regulation of PMN persistence is also discussed and evidence provided that persistence of PMN in B6 cornea is regulated by CD4+ T cells, while macrophages regulate PMN number in the cornea of BALB/c mice. The studies provide a better understanding of the inflammatory mechanisms that are operative in the cornea after P. aeruginosa challenge and are consistent with long-term goals of providing targets for alternative or adjunctive treatment for this disease. Future studies will be aimed at better defining the role of Toll receptors, neuropeptides (as unconventional modulators of the immune response) and exploitation of disease control by new techniques, such as RNA silencing.
Hazlett
Linda Dondero
LD
Department of Anatomy and Cell Biology, Wayne State University, 540 E Canfield, Room 7341, Detroit, MI 48201, USA. lhazlett@med.wayne.edu
D000818:Animals; D018925:Chemokines / Q000502:physiology; D003315:Cornea / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000502:physiology; D015818:Eye Infections, Bacterial / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007109:Immunity; D007634:Keratitis / Q000276:immunology* / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D018925:Chemokines; D016207:Cytokines