Cervicovaginal microbiota-host interaction modulates Chlamydia trachomatis infection

Epidemiological studies indicate the presence of numerous Lactobacillus provide a barrier to pathogens including Chlamydia trachomatis (CT), however the mechanisms elicited by the vaginal microbiota to alleviate risks of STI acquisition remain unknown. We conducted a culture-independent metataxonomic analysis on a cohort of women with genital CT infections during antibiotic treatment. These analyses informed experiments using a 3D model of cervical epithelial cells that examined the impact of Lactobacillus spp. culture supernatants on chlamydial susceptibility. A machine learning approach identified host miRNAs expressed in vivo while in vitro RNAseq analysis discovered specific host functions affected upon exposure to Lactobacillus spp. culture supernatants. Culture supernatants lacking D(-) lactic acid were not fully protective against CT infections since D(-) lactic acid acts as an effector molecule decreasing epithelial cell proliferation leading to attenuated CT infections. Transcriptomic analysis indicated additional epigenetic modifications though histone deacetylase-controlled mechanisms. This study highlights mechanisms by which the cervicovaginal microbiota protect against CT infections and can be leveraged into developing protective strategies.