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A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome

Nyaradzo T L Chigorimbo-Murefu1, Matthys Potgieter2,3, Sonwabile Dzanibe4

  • 1Divisions of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

Frontiers in Microbiology
|November 3, 2022
PubMed

Insights

Asymptomatic Chlamydia trachomatis infections alter the foreskin proteome, increasing inflammation and immune activation. This suggests a weakened genital tract barrier, potentially raising human immunodeficiency virus (HIV) acquisition risk in men.

Area of Science:

  • Urology
  • Immunology
  • Infectious Diseases

Background:

  • Limited data exists on asymptomatic sexually transmitted infections (aSTIs) and human immunodeficiency virus (HIV) acquisition risk in the male genital tract (MGT).
  • While foreskin removal (medical male circumcision) reduces HIV acquisition, the underlying molecular mechanisms remain unclear.

Purpose of the Study:

  • To investigate the impact of asymptomatic urethral Chlamydia trachomatis (CT) infection on the foreskin proteome.
  • To identify molecular changes in the foreskin associated with increased HIV acquisition risk.

Main Methods:

  • A shotgun liquid chromatography-tandem mass spectrometry (MS)-based proteomics approach was used.
  • Foreskins from 16 aSTI+ men and 10 STI- controls undergoing medical male circumcision (MMC) were analyzed.
  • A bioinformatic metaproteomic pipeline identified differentially expressed (DE) proteins and enriched functional pathways.

Main Results:

  • Asymptomatic CT infection significantly altered foreskin proteome composition.
  • Proteins linked to inflammation, immune activation, neutrophil degranulation, and viral evasion were enriched in aSTI+ individuals.
  • Homotypic cell-cell adhesion proteins were enriched in STI- controls, suggesting compromised barrier integrity in aSTI+ men.

Conclusions:

  • Asymptomatic urethral STIs cause significant epithelial tissue alterations in the foreskin.
  • These changes involve depleted barrier integrity and heightened immune activation, potentially increasing susceptibility to HIV acquisition.
Keywords:
HIV susceptibilityasymptomatic sexually transmitted infectionforeskinforeskin proteomegene ontology enrichment analysis

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