The role of type IV pilus in the interaction of Neisseria gonorrhoeae with a corneal epithelium tissue model

Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, can infect intact corneal epithelium, leading to inflammation, corneal perforation, and blindness. Models for studying this type of gonococcal infection are few and limited. We have tested stratified, polarized cornea models based on an immortalized hTCEpi corneal epithelium cell line for infection research using four derivatives of the N. gonorrhoeae MS11 strain that differ in pilus expression. We show that bacterial adherence depends on the functional type IV pilus in the early stages of infection, and that the formation of bacterial microcolonies and biofilms on the model surface leads to tissue destruction. The infection induces a specific cytokine response characterized by an increase in the secretion of IL-8 and tumor necrosis factor (TNF)-α, but not of IL-6. The testing of trifluoperazine, a drug that induces pilus retraction, on infected corneal tissue models showed that the drug strongly diminished the number of adherent gonococci only when applied simultaneously with bacteria, and not when bacteria were allowed to form microcolonies on the tissue surface. Our work describes, for the first time, hTCEpi-based corneal epithelium tissue models as a useful tool for investigating N. gonorrhoeae infection, with potential for application in high-throughput studies and drug screening.