Abstract
Chlamydia trachomatis (CT) is a highly prevalent bacterial sexually transmitted infection (STI), associated with severe disease complications. CT targets a unique immunological environment: the genital tract epithelium. Although sampling the genital tract is challenging, previous studies have shown that genital CT-specific antibodies exhibit enhanced neutralizing capacity compared with serum antibodies. Furthermore, tissue-resident memory T (TRM) cells provide superior protection compared with circulating T cells. However, further research is required to identify correlates of protection and explore correlations between local and systemic responses. This review provides an overview of the sampling methods suitable for identifying mucosal immune biomarkers associated with CT infection, as well as the immunoassays used. We identified the microbiome, presence of coinfections, hormonal influences, genetics, and CT infection state, load, and genotype as confounding factors to be considered in trial design. Finally, we discuss challenges related to the detection of mucosal immune biomarkers and offer recommendations for future research.