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Penile bacteria associated with HIV seroconversion, inflammation, and immune cells
Jessica L. Prodger, Alison G. Abraham, Aaron A.R. Tobian, Daniel E. Park, Maliha Aziz, Kelsey Roach, Ronald H. Gray, Lane Buchanan, Godfrey Kigozi, Ronald M. Galiwango, Joseph Ssekasanvu, James Nnamutete, Joseph Kagaayi, Rupert Kaul, Cindy M. Liu
Jessica L. Prodger, Alison G. Abraham, Aaron A.R. Tobian, Daniel E. Park, Maliha Aziz, Kelsey Roach, Ronald H. Gray, Lane Buchanan, Godfrey Kigozi, Ronald M. Galiwango, Joseph Ssekasanvu, James Nnamutete, Joseph Kagaayi, Rupert Kaul, Cindy M. Liu
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Research Article AIDS/HIV

Penile bacteria associated with HIV seroconversion, inflammation, and immune cells

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Abstract

The foreskin is a site of heterosexual acquisition of HIV-1 among uncircumcised men. However, some men remain HIV-negative despite repeated, unprotected vaginal intercourse with HIV-positive partners, while others become infected after few exposures. The foreskin microbiome includes a diverse group of anaerobic bacteria that have been linked to HIV acquisition. However, these anaerobes tend to coassociate, making it difficult to determine which species might increase HIV risk and which may be innocent bystanders. Here, we show that 6 specific anaerobic bacterial species, Peptostreptococcus anaerobius, Prevotella bivia, Prevotella disiens, Dialister propionicifaciens, Dialister micraerophilus, and a genetic near neighbor of Dialister succinatiphilus, significantly increased cytokine production, recruited HIV-susceptible CD4+ T cells to the inner foreskin, and were associated with HIV acquisition. This strongly suggests that the penile microbiome increases host susceptibility to HIV and that these species are potential targets for microbiome-based prevention strategies.

Authors

Jessica L. Prodger, Alison G. Abraham, Aaron A.R. Tobian, Daniel E. Park, Maliha Aziz, Kelsey Roach, Ronald H. Gray, Lane Buchanan, Godfrey Kigozi, Ronald M. Galiwango, Joseph Ssekasanvu, James Nnamutete, Joseph Kagaayi, Rupert Kaul, Cindy M. Liu

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Figure 2

High abundance of BASIC species, but not overall bacterial load, is associated with high foreskin T cell density without alterations in T cell subset distribution.

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High abundance of BASIC species, but not overall bacterial load, is asso...
Men in the cellular immunology cohort were divided into 3 groups, high BASIC species (group A, n = 12), high control taxa (group B, n = 12), and low BASIC species (group C, n = 19), and total bacterial density (A), BASIC species density (B), and subpreputial IL-8 (C), were compared. Foreskin T cell immune response was measured using flow cytometry (D) combined with CD3 immunohistochemistry (E) (analysis area highlighted in orange; scale bar: 250 μm [left and middle]; 200 μm [right]), and showed that group A had significantly (both P < 0.05) higher foreskin T cell density than groups B or C (F). Numbers in F represent percentages of CD3+ cells that are CD4+CCR5+ and Th17 cells (Wilcoxon rank-sum test).

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