The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field
- PMID: 28893286
- PMCID: PMC5594533
- DOI: 10.1186/s12981-017-0167-6
The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field
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.
Keywords: Chemokines; Circumcision; Foreskin; HIV-1; Microbiome; T-cells.
References
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- Dinh MH, Anderson MR, McRaven MD, Cianci GC, McCoombe SG, Kelley ZL, Gioia CJ, Fought AJ, Rademaker AW, Veazey RS, et al. Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission. PLoS Pathog. 2015;11(3):e1004729. doi: 10.1371/journal.ppat.1004729. - DOI - PMC - PubMed
-
- Dinh MH, Hirbod T, Kigozi G, Okocha EA, Cianci GC, Kong X, Prodger JL, Broliden K, Kaul R, Serwadda D, et al. No difference in keratin thickness between inner and outer foreskins from elective male circumcisions in Rakai, Uganda. PLoS ONE. 2012;7(7):e41271. doi: 10.1371/journal.pone.0041271. - DOI - PMC - PubMed
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