Kinetics of infection and local immune response in a model of chlamydia trachomatis conjunctival infection

Abstract

Aims/Purpose: Trachoma is caused by Chlamydia trachomatis conjunctival infections and evolves in two phases: i) active or acute trachoma caused by repeated infections and ii) scarring or chronic trachoma leading to conjunctival scarring, eyelid malposition, and corneal opacification. It remains the first cause of infectious blindness in developing countries. The purpose of this study was to precisely describe the kinetics of infection and local immune response in a non‐human primate model of acute trachoma.Methods: Cynomolgus Macaques received a single conjunctival inoculation of B/Tunis‐864 strain (104 IFU) and were assessed at weeks 2, 4, 6, 9, and 11. Clinical evaluation was performed by 3 independent masked observers on standardized ocular surface photographs graded using specific scores for both inflammation and follicles. Local immune response was assessed using multiparameter flow cytometry of conjunctival cells eluted from conjunctival prints. Tears cytokines were quantified using bead‐based Luminex multiplex assay. Bacterial quantification in conjunctival fluids was performed with quantitative PCR.Results: All animals (n = 12) developed typical follicular conjunctivitis (n = 12). The first 4 weeks post‐exposure were characterized by a conjunctival T cell influx (63% of CD45+ cells at week 3), with elevated interleukins 4, 8, and 5. In the later phase, after 9 weeks, we observed an influx of monocytes (53,2% of CD45+ cells at week 11) with reduced immune cells and a return to the initial cytokines level.Conclusion: This model faithfully mimics trachoma's acute phase. Local immunologic assays showed an early lymphocyte response with long‐term persistence of innate immune effectors. It offers an opportunity to assess potential preventive therapeutic strategies. Further studies, including implementing repeated bacterial conjunctival inoculations, are warranted to investigate the later stages of the diseases.