Research Article: The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field

Date Published: September 12, 2017

Publisher: BioMed Central

Author(s): Jessica L. Prodger, Rupert Kaul.

http://doi.org/10.1186/s12981-017-0167-6

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.

Partial Text

In summary, we hypothesize that immune activation in foreskin tissues adjacent to the sub-preputial space facilitates HIV 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, and that the genital microbiome may be an important driver of this immune activation. It might appear that understanding these mechanisms would be a moot point for men who undergo circumcision, but since circumcision is only 60% protective against HIV acquisition, it is possible—or even probable—that similar mechanisms underpin their residual HIV susceptibility, as well as HIV susceptibility in women. Therefore, 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 in HIV prevention.

 

Source:

http://doi.org/10.1186/s12981-017-0167-6

 

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