4.7 Article

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 220, Issue 2, Pages 330-339

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz087

Keywords

Chlamydia trachomatis; inflammatory disease; cytokines; risk factor

Funding

  1. National Institute of Allergy and Infectious Diseases (NIAID) [R01 AI119164, U19 AI084024, U19 AI113170, T32 AI007001]
  2. NIAID [UC6-AI058607]

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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 48 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 interleukin (IL) 15/CXCL10 (odds ratio [OR], 0.55 [95% confidence interval {CI}, .37-.78]), IL-16/tumor necrosis factor-alpha (OR, 0.66 [95% CI, .45-.93]), and CXCL14/IL-17A (OR, 0.73 [95% CI, .54-.97]) cytokine ratios were significantly (P <= .05) associated with decreased odds of endometrial infection. A higher Flt-3L/IL-14 ratio was significantly (P = .001) associated with a decreased risk of reinfection (hazard ratio, 0.71 [95% CI, .58-.88]). Conclusions. Cytokines involved in humoral, type I interferon, and T-helper (Th) 17 responses were associated with susceptibility to C. trachomatis, whereas cytokines involved in Th1 polarization, recruitment, and activation were associated with protection against ascension and reinfection.

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