Foreskins, Bacteria and HIV acquisition

 Cindy Liu from the Milken Institute School of Public Health, George Washington University presented her findings on the relationship between the penile microbiome and HIV susceptibility. Liu hypothesized that the penile microbiome drives pro-inflammatory responses and in turn increases HIV acquisition.

 The space underneath the foreskin is a unique environment with a characteristic microbiome. Analysing subpreputial swabs from men in Uganda, Liu and her colleagues used molecular techniques to investigate bacterial populations prior to and after male circumcision. 16S rRNA sequencing was employed to characterise bacteria to genus level, and a pan-bacterial DNA RT-PCR was used to quantify total bacterial load. Together, these were used to estimate the absolute abundance of specific bacterial taxa in the subpreputial space.

Prior to circumcision, the subpreputial space was characterised by a diverse bacterial community that varied between individuals and over timel. A wide variety of anaerobes, including Prevotella, Finegoldia, Peptoniphilius, and Aerococcus, were isolated in high numbers. Post-circumcision, the populations of these anaerobes reduced, and resembled flora from other skin. Anaerobes decreased, populations became less variable, and Lactobacilli increased.

 Expanding on this, the investigators examined the immunological responses to these changes in the microbiome. Langerhan cells, the antigen-presenting cells par excellence of mucosal surfaces, are thought to be integral to HIV acquisition. In the inactivated resting state, Langerhan cells ingest HIV virions, and lyse them prior to presenting the lysed products to lymphocytes at the lymph node. In activated Langerhan cells however, degradation of HIV virions is bypassed, resulting in presentation of intact virus to nodal lymphocytes and the commencement of viral replication. Anaerobic flora were postulated to be triggers for Langerhan cell activation.

  Liu found that IL-8, one of the key cytokines implicated in immune activation, was significantly higher among men colonised by Prevotella, and other key anaerobic organisms.  IL-8 is known to attract neutrophils along a chemotactic gradient, and induce them to release MIP 3a alpha and MCP-1, which in turn lead to recruitment and activation of CD4+ T lymphocytes, drawing them closer to the epithelial surface.

 This work supports the hypothesis that an anaerobic subpreputial microbiome induces pro-inflammatory local immune responses, and that these changes are negated by male circumcision.

 Further work on the correlation between the penile microbiome and HIV acquisition is keenly awaited. Liu’s current collaboration with the Kirby Institute will examine the role of the ‘dorsal slit’ modified circumcision commonly practiced in parts of PNG, and will hopefully give insight into this cultural practice’s potential role in HIV prevention.