Type IV Pili ofNeisseria gonorrhoeaeInfluence the Activation of Human CD4+T Cells

Abstract

Neisseria gonorrhoeaeis the causative agent of the sexually transmitted disease gonorrhea, and infection with this organism is typically associated with an intense inflammatory response. In many individuals, however, the infection is asymptomatic and can progress to serious secondary complications. The type IV pili ofNeisseria gonorrhoeaemediate binding of the bacteria to host cells and are involved in cellular signal transduction. In these studies we have demonstrated that gonococcal pili influence human CD4⁺T cells by using isogenic strains ofN. gonorrhoeaewith piliated and nonpiliated phenotypes. To determine the impact of piliation on the cellular status, we examined the expression of activation markers, cellular proliferation, and the production of cytokines after infection. The activation marker CD69 showed significantly increased expression on cells infected with the piliated strain, and this expression was dependent on costimulation of the T-cell receptor. Infection with piliated gonococci also altered T-cell proliferation and influenced the production of the regulatory cytokine interleukin-10. PilC, the putative pilus adhesin, was also observed to influence cellular activation but had no impact on the proliferation of cells further indicating that pilus-mediated adhesion is important in gonococcal stimulation of CD4⁺T cells. These results show that the piliation status of gonococci influences CD4⁺T-cell activation and that the adhesion mediated by pilus components aids in the regulation of the T-cell response toN. gonorrhoeae.