Taylor B Poston1, De'Ashia E Lee2, Toni Darville1, Wujuan Zhong3, Li Dong3, Catherine M O'Connell1, Harold C Wiesenfeld4, Sharon L Hillier4, Gregory D Sempowski5,6, Xiaojing Zheng1. 1. Department of Pediatrics, University of North Carolina at Chapel Hill. 2. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill. 3. Department of Biostatistics, University of North Carolina at Chapel Hill. 4. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine and the Magee-Womens Research Institute Pittsburgh, Pennsylvania. 5. Departments of Medicine and Pathology, Durham, North Carolina. 6. Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina.
Abstract
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-α (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.
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-α (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.
Authors: Xiaojing Zheng; Catherine M O'Connell; Wujuan Zhong; Taylor B Poston; Harold C Wiesenfeld; Sharon L Hillier; Maria Trent; Charlotte Gaydos; George Tseng; Brandie D Taylor; Toni Darville Journal: Front Cell Infect Microbiol Date: 2018-09-20 Impact factor: 5.293
Authors: Scott H Randell; Toni Darville; Uma M Nagarajan; Bryan E McQueen; Amy Kiatthanapaiboon; M Leslie Fulcher; Mariam Lam; Kate Patton; Emily Powell; Avinash Kollipara; Victoria Madden; Robert J Suchland; Priscilla Wyrick; Catherine M O'Connell; Boris Reidel; Mehmet Kesimer Journal: Infect Immun Date: 2020-08-19 Impact factor: 3.441