Upregulation of ATF 3 inhibits expression of the pro‐inflammatory cytokine IL ‐6 during N eisseria gonorrhoeae infection

Summary N eisseria gonorrhoeae regulates the expression of epithelial cell genes, activates cytoprotective pathways in the infected cell and protects it from apoptosis. Many of these responses are enhanced by the T ype IV pilus ( Tfp ). We tested the hypothesis that N . gonorrhoeae modulates the innate immune response by inducing expression of ATF 3, a transcription factor that negatively regulates the expression of many cytokine genes. We further determined whether Tfp are involved in these events. We found that N . gonorrhoeae induces ATF 3 expression in mucosal epithelial cells through activation of mitogen‐activated protein kinases. Maximal ATF 3 expression requires Tfp retraction. Knocking down endogenous levels of ATF 3 results in higher levels of IL ‐6 transcript. Our findings strongly suggest that ATF 3 is involved in suppressing cytokine expression during gonococcal infection. We propose a model for the role of ATF 3 in the context of N . gonorrhoeae infection.