Cervical cytokines associated with Chlamydia trachomatis susceptibility and protection.

BACKGROUND: Chlamydia trachomatis can cause reproductive morbidities after ascending to the upper genital tract of women, and repeated infection can lead to worse disease. Data related to protective immune responses at the cervical mucosa that could limit chlamydial infection to the cervix and/or prevent reinfection inform vaccine approaches and biomarkers of risk.

METHODS: We measured forty-eight cytokines in cervical secretions from women having chlamydial cervical infection alone (N=92) or both cervical and endometrial infection (N=68). Univariable regression identified cytokines associated with differential odds of endometrial infection and reinfection risk, and multivariable stepwise regression identified cytokine ratios associated with differential risk.

RESULTS: Elevated IL-15/CXCL10 [odds ratio (OR), 0.55; 95% confidence interval (CI), 0.37-0.78], IL-16/TNFα [OR, 0.66 (95% CI, 0.45-0.93)], and CXCL14/IL-17A [OR, 0.73 (95% CI, 0.54-0.97)] cytokine ratios were significantly (P≤0.05) associated with decreased odds of endometrial infection. A higher Flt-3L/IL-14 ratio was significantly (P=0.001) associated with a decreased risk of reinfection [hazard ratio, 0.71 (95% CI, 0.58-0.88)].

CONCLUSIONS: Cytokines involved in humoral, type-1 interferon, and Th17 responses were associated with susceptibility to C. trachomatis, while cytokines involved in Th1 polarization, recruitment, and activation were associated with protection against ascension and reinfection.