Cervicovaginal inflammation and HIV target cell activation in adolescent girls and young women with Chlamydia trachomatis infections

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Abstract Background Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by Chlamydia trachomatis (CT) infections, a leading cause of pelvic inflammatory disease (PID), infertility, and increased HIV susceptibility. CT-induced genital inflammation disrupts mucosal barriers and activates HIV target cells, compounding reproductive and immunological risks. We investigated the impact of CT infection in AGYW from two South African regions, focusing on genital inflammation and immune activation. Methods An observational cohort of 298 sexually active AGYW (16–22 years) from Cape Town and Johannesburg was enrolled. Participants in Johannesburg attended a single study visit, while those in Cape Town were followed longitudinally for up to three visits over 6–8 months. Cytokine profiling of cervicovaginal samples assessed inflammatory responses, while cervical cytobrush-derived CD4+ T cells were analyzed for CD38, Ki67 and CCR5 expression. CT ompA genotyping examined strain diversity. Results CT prevalence was 2.4 times higher in Cape Town (41.6%) than in Johannesburg (17.4%). Infection with CT led to an upregulation of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, with a stronger inflammatory response observed in Johannesburg. Genotypic analysis revealed regional variation: genovar D, predominant in Cape Town, was associated with lower IFN-γ concentrations, whereas genovar E, more common in Johannesburg, was associated with higher IFN-γ levels. AGYW who experienced CT infection across multiple study visits did not exhibit elevated genital tract cytokine levels compared to those with a single infection. However, they did show an increase in activated and proliferating cervical CD4+ T cells, which may contribute to heightened HIV susceptibility. Conclusions CT genotypic diversity and regional variation are associated with differences in immune responses in AGYW, alongside important contributions from host immune history. These findings support the need for integrated sexual health services and inform future regionally relevant vaccine strategies.

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