Investigating the Correlation of Chlamydia Trachomatis-Specific Cytokines with Risk for Chlamydia Reinfection

Background:  Chlamydia trachomatis (CT) infection can lead to reproductive morbidity in women. Despite chlamydia control efforts, the prevalence of CT infection in the U.S. remains high. Animal models suggest that protection against CT is mediated through IFN-γ produced by CD4⁺ T-cells, but human correlates of protection remain to be elucidated. We investigated the association of CT-specific cytokines with frequency of CT reinfection.

Methods:  In an ongoing prospective study of women presenting to an urban STD clinic for treatment of a positive chlamydia screening nucleic acid amplification test (NAAT), enrolled subjects receive azithromycin 1g and then return for 3-month and 6-month follow-up visits for repeat CT NAAT to evaluate for CT reinfection. At all study visits, subjects provide blood for peripheral blood mononuclear cell (PBMCs) isolation. Baseline PBMCs from subjects with vs. without subsequent CT reinfection were stimulated with CT antigen PGP3 and elementary bodies (EB) in vitro for 72hrs, followed by collection of supernatant.  Measurement of 12 different cytokines was performed using multiplex technology (V-Plex®, Meso Scale Discovery). Cell media and phytohemagglutinin were used as negative and positive controls, respectively. We evaluated for associations of cytokine production with CT reinfection frequency using the Mann-Whitney U test.

Results:  To date, cytokines have been measured at baseline in 39 women: 13 with vs. 26 without subsequent CT reinfection. Most pro-inflammatory cytokines (IFN-g, TNF-a, IL-8 etc.) were expressed at high concentrations. IL-2 expression was low. Compared with women without CT reinfection at follow-up (n=26), a higher proportion with subsequent reinfection (n=13) had higher levels of the immunomodulatory cytokines IL-10 and IL-13. 

Conclusions:  Women who had subsequent CT reinfection had higher levels of the immunomodulatory cytokines IL-10 and IL-13 at the time of treatment, which suggests these cytokines may play a role in preventing development of protective immunity.