Neisseria gonorrhoeae is the etiological agent of the disease gonorrhea and a major co-factor in HIV-1 infection.  Teenagers and young adults are at high risk for infection, which is unsettling in view of the increased risk for HIV-1 infection associated with gonorrhea.  Women suffer a disproportionate burden of health complications associated with N. gonorrhoeae infection.  Infection in men develops as an acute urethritis; however, infection in women typically is asymptomatic, often leading to ascending infection and chronic disease sequelae.  Consistent with the different clinical presentations of gonococcal infection observed between men and women, the pathogenic mechanisms and the human receptors mediating infection also differ.   The high frequency with which these bacteria alter their cell surface constituents and the varied mechanisms that they use to invade host cells has made vaccine development extremely problematic.   The presence of complement receptor type 3 (CR3) on epithelial of the female tract and engagement of this receptor leading to membrane ruffling are novel findings.  Currently, there are no data defining putative effector molecules mediating ruffling triggered by CR3 engagement and few studies have examined signal transduction in (primary) epithelial cells.  Our data suggest that secreted gonococcal products mediate these processes by interacting with cervical cell proteins and subverting their function.  This suggests that a dynamic interplay between host and bacterial constituents in potentiating gonococcal disease.  These processes are further complicated by cyclic environmental changes, which occur within the female genital tract.  A major focus of our future work will be to further characterize the host and bacterial factors and responses required for successful gonococcal infection of cervical epithelia.  We are interested in further delineating the signal transduction cascades initiated with cervical gonococcal infection, in analyzing the cyclic contribution of complement and of hormones to these processes, and in examining the oxidative and non-oxidative defenses potentially generated by cervical epithelia with gonococcal challenge. We are also interested in determining if the complement-gonococcus-cervical interaction is unique or if this aberrant complement-microbe interaction occurs between other mucosal surfaces (e. g. airway epithelium) and bacteria (e. g. Neisseria meningitidis type B and Bordetella pertussis).   Although these queries are rooted in cellular microbiology, we use a wide variety of approaches to explore these questions.  By further elucidating (at the molecular and cellular level) host and bacterial factors and responses facilitating infection, it may be possible to identify new vaccine candidates or to develop new therapeutic strategies for better disease management and improved women’s health.