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

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, infertility and increased HIV susceptibility. CT-induced genital inflammation disrupts mucosal barriers and activates HIV target cells, compounding immunological risks. We investigated 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 (aged 16–22 years) from Cape Town and Johannesburg was enrolled. Participants in Johannesburg attended one visit, while those in Cape Town were followed longitudinally (6–8 months). Cytokine profiling of cervicovaginal samples assessed inflammatory responses, while cervical cytobrush-derived CD4+ T cells were analysed for CD38, Ki67 and C-C chemokine receptor type 5 expression. CT ompA genotyping examined strain diversity. Results CT prevalence was 2.4-times higher in Cape Town (41.6%) than Johannesburg (17.4%). CT infection was associated with upregulated interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, with responses appearing stronger in Johannesburg, although low CT cases at this site limited regional comparisons. Genotyping suggested regional variation: genovar D, predominant in Cape Town, was associated with lower interferon (IFN)-γ concentrations, whereas genovar E, more common in Johannesburg, was associated with higher IFN-γ concentrations. AGYW with CT infection across multiple visits did not exhibit elevated genital tract cytokine levels compared with those infected at a single visit. However, they showed increased activated cervical CD4+ T cells. Conclusions CT-associated immune responses in AGYW appear to reflect a combination of pathogen diversity, regional context and host immune history.