Topical neutralization of interleukin-17 during experimental Pseudomonas aeruginosa corneal infection promotes bacterial clearance and reduces pathology.
The proinflammatory cytokine interleukin-17 (IL-17) is involved in neutrophilic tissue infiltration, contributing to both microbial clearance as well as inflammation-associated tissue damage. Its role during bacterial corneal infections is unknown. We hypothesized that IL-17 responses would be detrimental in this setting and tested the impact of IL-17 receptor deficiency or antibody-mediated neutralization of IL-17 in a murine model of Pseudomonas aeruginosa ulcerative keratitis after scratch injury. We found that, compared with infected corneas from wild-type mice, those from IL-17 receptor (IL-17R)-deficient mice had significantly lower corneal pathology scores, neutrophil influx, and intracellular bacterial levels. Infected IL-17R-deficient corneas had low intercellular adhesion molecule 1 (ICAM-1) expression, and ICAM-1-deficient mice were similarly resistant to infection. Topical treatment with polyclonal antibodies to IL-17 resulted in significant reductions in corneal pathology and also lowered bacterial counts after infection with six different laboratory or clinical P. aeruginosa strains, including both invasive and cytotoxic strains. Thus, neutralization of IL-17 during P. aeruginosa corneal infection reduces neutrophil influx and pathology without compromising bacterial clearance and offers a promising new avenue for therapy of these potentially sight-threatening infections.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Tanweer S
TS
Zaidi
Tauqeer
T
Zaidi
Gerald B
GB
Pier
Gregory P
GP
Priebe
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D003320:Corneal Ulcer / Q000382:microbiology* / Q000473:pathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism
D057134:Antibodies, Neutralizing; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D018799:Intercellular Adhesion Molecule-1