The biology of how circumcision reduces HIV susceptibility: Broader implications for the prevention field

Jessica L. Prodger, Rupert Kaul

Research output: Contribution to journalReview articlepeer-review

Abstract

Circumcision reduces heterosexual HIV-1 acquisition in men by at least 60%. However, the biological mechanisms by which circumcision is protective remain incompletely understood. We test the hypothesis that the sub-preputial microenvironment created by the foreskin drives immune activation in adjacent foreskin tissues, facilitating HIV-1 infection through a combination of epithelial barrier disruption, enhanced dendritic cell maturation, and the recruitment/activation of neutrophils and susceptible CD4 T cell subsets such as Th17 cells. Furthermore, we provide evidence that the genital microbiome may be an important driver of this immune activation. This suggests that new modalities to reduce genital immune activation and/or alter the genital microbiome, used alone or in combination with topical microbicides, may be of significant benefit to HIV prevention.

Original languageEnglish (US)
Article number49
JournalAIDS research and therapy
Volume14
Issue number1
DOIs
StatePublished - Sep 12 2017

Keywords

  • Chemokines
  • Circumcision
  • Foreskin
  • HIV-1
  • Microbiome
  • T-cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Virology
  • Pharmacology (medical)

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