Physiological Levels of Estrogen and Progesterone Modulate CR3 expression on, and Neisseria gonorrhoeae Infection of, Primary, Human, Cervical Epithelial Cells

Abstract

Despite advances made in our understanding of Neisseria gonorrhoeae pathogenesis, factors dictating the divergent presentation of gonococcal disease observed between men and women, in vivo, remain unclear. Clinical data indicate that gonococcal pathogenesis of the female genital tract is influenced by steroid hormones. Notwithstanding, there are limited data addressing how steroid hormones modulate gonococcal pathogenesis. Hence, we investigated the effect(s) of physiological concentrations of estrogens and progestogens on N. gonorrhoeae viability and on complement-mediated infection of primary cervical cells. In contrast to previous studies that showed a bacteriostatic effect of non-physiological concentrations of steroid hormones on gonococci, our data indicate that physiological concentrations of estrogens and progestogens do not inhibit gonococcal growth in vitro or during infection of primary cervical cells. Estradiol promoted complement receptor 3 recruitment to the cervical cell surface and, thus, the ability of gonococci to associate with these cells. Progesterone-predominant assay conditions resulted in decreased expression of Opa proteins by gonococci, increased complement production by cervical cells, and increased iC3b opsonization of gonococci during cervical cell challenge. Collectively, our data support clinical observations and demonstrate that estrogens and progestogens distinctly modulate gonococcal cervical infection.