Gallouët, A.-S. | bioRxiv Science

bioRxiv2025

The vaginal microbiota composition influences cervicovaginal and systemic inflammation induced by Chlamydia trachomatis infection.

BackgroundChlamydiosis, a sexually transmitted infection (STI) induced by Chlamydia trachomatis (CT), increases local inflammation (cytokine production, recruitment of immune cells such as neutrophils). Few is known on the impact of CT infection on the phenotype of cervicovaginal neutrophils. Vaginal microbiota (VM) is a key factor in the regulation of local immune responses and STI acquisition where Lactobacillus spp are associated with protection. In this study, the VM of cynomolgus macaques was enriched with Lactobacillus crispatus after local metronidazole treatment followed by repeated intravaginal inoculations of CT. VM composition, CT infection and local and systemic inflammation were monitored. ResultsFirst, we observed that metronidazole treatment induced drastic modifications of the VM by reducing the abundance of several anaerobes and increasing the number of natural Lactobacillus spp (Lactobacillus johnsonii and its prophage mainly) as well as opportunistic bacteria (Streptococcus spp and Staphylococcus spp). After CT exposure of L. crispatus treated or not animals, a non-persisting CT infection and no association between L. crispatus enrichment and a lower susceptibility to CT infection were detected. However, the production of serum specific anti-CT IgG was higher in L. crispatus treated animals. Moreover, the production of anti-CT IgG was associated with various bacterial species. An increased production of peripheral blood cytokines after CT infection was observed in untreated animals, whereas L. crispatus treated animals exhibited an increased production of cervicovaginal cytokines. Peripheral blood neutrophils were more mature and activated after CT infection/inoculation in both groups. Very few alterations of the cervicovaginal neutrophil phenotype were noticed after CT infection. Markers expressed on neutrophils were associated with bacterial species and differences were detected according to groups. ConclusionThese results suggest a better local immune response as well as a better control on systemic inflammation upon CT infection in L. crispatus treated animals compared to untreated animals. Indeed, it highlight an impact of VM composition on the local and systemic immune responses induced by CT infection. This study confirmed that VM composition can be a powerful tool to modulate local inflammation and STI susceptibility.

immunology↗

bioRxiv2023

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

BackgroundTrachoma -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 FindingsThe 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/SignificanceOur 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. Author SummaryChlamydia trachomatis is the leading infectious cause of blindness worldwide. The pathogenesis of trachoma is more complicated than other types of bacterial conjunctivitis: clinical signs of trachoma are rooted in repeated Chlamydia trachomatis infections of the inner eyelid surfaces, which roughens the skin. This lead to eyelid deformation and lashes rubbing on the cornea, which across multiple years of abrasion, ends with corneal opacification. The immune system is a pivotal aspect of disease, involved in disease aggravation, but also key for exploitation in development of a trachoma vaccine. Here we describe a non-human primate model of trachoma that accurately reproduces acute human eye disease, allowing for the precise assessment of the local immune responses in infected eyes. A progressing immune response occurred 4 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.

microbiology↗