Topical Neutralization of Interleukin-17 during Experimental Pseudomonas aeruginosa Corneal Infection Promotes Bacterial Clearance and Reduces Pathology

Abstract

ABSTRACTThe 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 ofPseudomonas aeruginosaulcerative 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 clinicalP. aeruginosastrains, including both invasive and cytotoxic strains. Thus, neutralization of IL-17 duringP. aeruginosacorneal infection reduces neutrophil influx and pathology without compromising bacterial clearance and offers a promising new avenue for therapy of these potentially sight-threatening infections.