Multimodal mucosal and systemic immune characterization of a novel non-human primate trachoma model highlights the critical role of local immunity during acute phase disease

Background: Trachoma -the leading cause of blindness worldwide as a result of infection- is caused by repeated Chlamydia trachomatis (Ct) conjunctival infections. Disease develops in two phases: i) active (acute trachoma, characterized by follicular conjunctivitis), then long-term ii) scarring (chronic trachoma, characterized by conjunctival fibrosis, corneal opacification and eyelid malposition). Scarring trachoma is driven by the number and the severity of reinfections. The immune system is a pivotal aspect of disease, involved in disease aggravation, but also key for exploitation in development of a trachoma vaccine. Therefore, we characterized clinical and local immune response kinetics in a non-human primate model of acute conjunctival Ct infection and disease. Methodology/Principal Findings: The conjunctiva of non-human primate (NHP, Cynomolgus monkeys -Macaca fascicularis-) were inoculated with Ct (B/Tunis-864 strain, B serovar). Clinical ocular monitoring was performed using a standardized photographic grading system, and local immune responses were assessed using multi-parameter flow cytometry of conjunctival cells, tear fluid cytokines, immunoglobulins, and Ct quantification. Clinical findings were similar to those observed during acute trachoma in humans, with the development of typical follicular conjunctivitis from the 4th week post-exposure to the 11th week. Immunologic analysis revealed an early phase influx of T cells in the conjunctiva and elevated interleukins 4, 8, and 5, before a later phase monocytic influx accompanied by a decrease in other immune cells, and tear fluid cytokines returning to initial levels. Conclusion/Significance: Our NHP model accurately reproduces acute trachoma clinical signs, allowing for the precise assessment of the local immune responses in infected eyes. A progressing immune response occurred for weeks after exposure to Ct, which subsided into persistence of innate immune responses. Understanding these local responses is the first step towards using the model to assess new vaccine and therapeutic strategies to prevent disease. ### Competing Interest Statement Funding for this work was recieved from the Thea foundation (EP, ML, AR). Additionnally roles of consultants and occasional speakers for the Thea foundation is disclosed (ML, AR). These competing interests do not alter adherence to PLOS policies on sharing data and materials.