Upregulation of ATF3 inhibits expression of the pro-inflammatory cytokine IL-6 during Neisseria gonorrhoeae infection

Summary: Neisseria 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 Type IV pilus (Tfp). We tested the hypothesis that N.gonorrhoeae modulates the innate immune response by inducing expression of ATF3, 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 ATF3 expression in mucosal epithelial cells through activation of mitogen-activated protein kinases. Maximal ATF3 expression requires Tfp retraction. Knocking down endogenous levels of ATF3 results in higher levels of IL-6 transcript. Our findings strongly suggest that ATF3 is involved in suppressing cytokine expression during gonococcal infection. We propose a model for the role of ATF3 in the context of N.gonorrhoeae infection.