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The Mucosal Cytokine Landscape of Acute Gonorrhea Using a Controlled Human Infection Model.
Michael P Motley1,2, Marcia M Hobbs2, Andreea Waltmann2
1Division of Infectious Diseases, Department of Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Medrxiv : the Preprint Server for Health Sciences
|March 11, 2026
Summary
Early gonorrhea infection in males triggers localized urethral inflammation with increased urine cytokines, but no systemic immune response. This highlights the potential of urine markers for studying local effects and developing anti-gonococcal immunity for vaccines.
Area of Science:
- Immunology
- Microbiology
- Vaccine Development
Background:
- Neisseria gonorrhoeae (gonorrhea) causes frequent reinfections, necessitating vaccine development.
- Understanding early host immune responses is crucial for anti-gonococcal vaccine strategies.
- Current knowledge of early mucosal immune responses to gonorrhea is limited.
Purpose of the Study:
- To investigate the local and systemic immune response to early Neisseria gonorrhoeae infection.
- To characterize cytokine profiles in urine and plasma during experimental gonorrhea urethritis.
- To assess the utility of a controlled human infection model for studying gonorrhea pathogenesis.
Main Methods:
- Utilized a controlled human infection model with male volunteers experimentally infected with N. gonorrhoeae.
- Collected urine and blood specimens before infection, during acute symptoms, and after treatment.
- Performed multiplex cytokine analysis on all specimens.
Main Results:
- All participants developed urethritis within 2-5 days post-inoculation.
- Urine cytokine levels (IL-1RA, G-CSF, CXCL10, CCL4, CCL11, GROα/β/γ, IL-8/CXCL8) increased significantly.
- Plasma cytokine levels remained unchanged, indicating a localized urethral response.
- Specific urine cytokines correlated with pyuria severity.
Conclusions:
- Early N. gonorrhoeae infection induces a localized immune response confined to the urethra.
- Urine cytokine analysis is a valuable non-invasive tool for studying local host responses.
- Findings support the use of human challenge models for gonorrhea research and vaccine development.
