Human foreskin proteome with aSTI

There is scant data on the mechanisms through which asymptomatic STIs (aSTIs) alter risk of HIV acquisition in the male genital tract. Foreskin removal lowers the risk of HIV acquisition, but molecular events leading to this protection are unclear. Here we show that an asymptomatic urethral infection with Chlamydia trachomatis significantly alters the foreskin epithelial proteome composition. We developed and optimised a shotgun liquid chromatography coupled tandem mass spectrometry based proteomics approach and applied this to foreskins collected at the time of medical male circumcision from 16 aSTI+ cis-gender men and 10 age-matched STI- controls. We used a novel bioinformatic metaproteomic pipeline to detect differentially expressed proteins. Gene enrichment ontology analysis revealed proteins associated with inflammatory and immune activation function in both inner and outer foreskin from men with an aSTI. Neutrophil activation/degranulation and viral-evasion proteins were significantly enriched in foreskins from men with aSTI whereas homotypic cell-cell adhesion proteins were enriched in foreskin tissue from men without an STI. Collectively, our data show that an asymptomatic urethral sexually transmitted infection result in profound alterations in epitheial tissue that potentially causes depletion of barrier integrity and function and that may encourage HIV susceptibilty.