Browsing by Author "Huibner, Sanja"

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    HIV Infection in Uncircumcised Men is Associated with Altered CD8 T-cell Function but Normal CD4 T-cell Numbers in the Foreskin
    (The Journal of infectious diseases, 2014) Prodger, Jessica L.; Hirbod, Taha; Gray, Ronald; Kigozi, Godfrey; Nalugoda, Fred; Galiwango, Ronald; Reynolds, Steven J.; Huibner, Sanja; Wawer, Maria J.; Serwadda, David; Kaul, Rupert; Rakai, Genital Immunology Research Group
    Human immunodeficiency virus (HIV)–infected (HIV+) men are more susceptible to sexually transmitted infections, and may be superinfected by HIV. We hypothesized that HIV induces immune alterations in the foreskin that may impact the subsequent acquisition/clearance of genital coinfections. Methods. Foreskin tissue and blood were obtained from 70 HIV-uninfected and 20 HIV+ men undergoing circumcision. T cells were characterized by flow cytometry, immunohistochemistry, and polymerase chain reaction. Results. There was substantial influx of CD8 T-cells into the foreskins of HIV+ men (108.8 vs 23.1 cells/mm2; P < .001); but foreskin CD4 T-cell density was unchanged (43.0 vs 33.7/mm2; P = .67), despite substantial blood depletion (409.0 vs 877.8 cells/μL; P < .001). While frequencies of foreskin C-C chemokine receptor type 5+ (CCR5+) T cells, T regulatory cells, and T-helper 17 cells were unaltered in HIV+ men, CD8 T-cell production of tumor necrosis factor α (TNFα) was decreased. HIV-specific CD8 T cells were present in the foreskins of HIV+ men, although their frequency and function was reduced compared to the blood. Conclusions. Foreskin CD4 T-cell density and CCR5 expression were not reduced during HIV infection, perhaps explaining susceptibility to HIV superinfection. Foreskin CD8 T-cell density was increased, but decreased production of TNFα may enhance susceptibility to genital coinfections in HIV+ men.
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    Immune milieu and microbiome of the distal urethra in Ugandan men: impact of penile circumcision and implications for HIV susceptibility
    (Microbiome, 2022) Galiwango, Ronald M.; Park, Daniel E.; Huibner, Sanja; Onos, Abigail; Aziz, Maliha; Roach, Kelsey; Anok, Aggrey; Nnamutete, James; Isabirye, Yahaya; Wasswa, John Bosco; Male, Deo; Kigozi, Godfrey; Tobian, Aaron A. R.; Prodger, Jessica L.; Liu, Cindy M.; Kaul, Rupert
    Coronal sulcus (CS) anaerobe abundance and IL-8 levels are linked to HIV acquisition, and are dramatically reduced after penile circumcision (PC). The distal urethra may be the site of some HIV acquisition before PC, and presumably most acquisition post PC. We describe the immune milieu and microbiome of the distal urethra in uncircumcised Ugandan men, and define the impact of PC. Participants consisted of HIV-negative, genital symptomfree adult Ugandan men undergoing PC (n = 51). Urethral and coronal sulcus swabs were collected at baseline and at 6- and 12-months post-PC. Soluble immune factors were quantified by multiplex ELISA, and bacterial abundance assessed by 16S rRNA qPCR and sequencing. Results: At baseline, the urethra was enriched compared to the CS for most cytokines (including IL-8 and MIP-1β) and soluble E-cadherin (sE-cadherin, an epithelial disruption marker), although CS levels of IL-1α and IL-1β were higher. Baseline total bacterial abundance was ≥ 20-fold higher in the CS than the urethra (median 27,100 vs. 1200 gene copies/swab, p = 0.001), and anaerobes comprised 58% of CS bacteria vs. 42% of urethral bacteria. PC did not alter urethral IL-8 (median 806 at baseline vs. 1130 pg/ml at 12 months; p = 0.062) and urethral sE-cadherin increased (113,223 vs. 158,385 pg/ml, p = 0.009), despite five- and sevenfold drops in total bacterial and anaerobe abundance after PC, respectively. However, PC dramatically reduced CS levels of sE-cadherin (15,843 vs. 837 pg/ml, p < 0.001) and most cytokines (IL-8; 34 vs. 3 pg/ml, p < 0.001), while reducing total bacterial and anaerobe abundance by 13-fold and 60-fold, respectively (both P ≤ 0.004). Conclusions: The urethra is immunologically rich with characteristics of an HIV-susceptible tissue site. However, PC had no impact on urethral immunology and may have reduced epithelial integrity, despite modest reductions in total bacteria and anaerobes, suggesting that HIV protection from PC is not mediated via immune or microbiome alterations in the urethra.