The host response to Neisseria gonorrhoeae varies considerably, as large cohort studies have identified subpopulations of individuals capable of spontaneously clearing gonococcal infection. Understanding the local immune factors associated with this clearance is critical for defining protective anti-gonococcal immunity and informing vaccine development. During our trial evaluating the efficacy of 4CMenB against experimental gonococcal infection, we observed that participants who did not develop infection rapidly cleared gonococci from the urethra, with most testing negative by urine nucleic acid amplification testing within one day of inoculation. We therefore sought to determine whether local gene expression signatures differ between participants who resisted infection and those who became infected, and whether specific transcriptional patterns may predict resistance.
First-void urine samples were collected from 18 participants enrolled in a Controlled Human Infection Model study before urethral challenge with N. gonorrhoeae strain FA1090 and again one day after inoculation. Of the participants included in the analysis, 10 developed urethritis characterized by urethral discharge and positive nucleic acid amplification testing, while 8 did not develop infection. RNA was isolated from urine pellets, and transcript abundance for 531 genes was quantified using the NanoString nCounter Host Response Panel.
Total RNA yield from urine pellets significantly increased between pre- and post-inoculation timepoints in participants who developed infection, whereas no significant increase was observed in participants who remained uninfected. Comparison of normalized post-inoculation transcript profiles between infected and uninfected individuals identified 46 genes with higher relative expression in infected participants (fold change >1.5), including IL23A, CCL20, CXCL3, IL6, IL1A, IL1B, and TNF, and 26 genes with lower relative expression (fold change <-1.5), including CD81, CD4, and CD86, . Additional analyses and results will be presented at the conference.