Immune milieu and microbiome of the distal urethra in Ugandan men: impact of penile circumcision and implications for HIV susceptibility

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dc.contributor.authorGaliwango, Ronald M.
dc.contributor.authorPark, Daniel E.
dc.contributor.authorHuibner, Sanja
dc.contributor.authorOnos, Abigail
dc.contributor.authorAziz, Maliha
dc.contributor.authorRoach, Kelsey
dc.contributor.authorAnok, Aggrey
dc.contributor.authorNnamutete, James
dc.contributor.authorIsabirye, Yahaya
dc.contributor.authorWasswa, John Bosco
dc.contributor.authorMale, Deo
dc.contributor.authorKigozi, Godfrey
dc.contributor.authorTobian, Aaron A. R.
dc.contributor.authorProdger, Jessica L.
dc.contributor.authorLiu, Cindy M.
dc.contributor.authorKaul, Rupert
dc.date.accessioned2022-10-26T13:04:08Z
dc.date.available2022-10-26T13:04:08Z
dc.date.issued2022
dc.description.abstractCoronal 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.en_US
dc.identifier.citationGaliwango, R. M., Park, D. E., Huibner, S., Onos, A., Aziz, M., Roach, K., ... & Kaul, R. (2022). Immune milieu and microbiome of the distal urethra in Ugandan men: impact of penile circumcision and implications for HIV susceptibility. Microbiome, 10(1), 1-13. https://doi.org/10.1186/s40168-021-01185-9en_US
dc.identifier.otherhttps://doi.org/10.1186/s40168-021-01185-9
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/5011
dc.language.isoenen_US
dc.publisherMicrobiomeen_US
dc.subjectMicrobiomeen_US
dc.subjectCytokinesen_US
dc.subjectCoronal sulcusen_US
dc.subjectPenile urethraen_US
dc.subjectPenile circumcisionen_US
dc.subjectUgandaen_US
dc.subjectHIVen_US
dc.titleImmune milieu and microbiome of the distal urethra in Ugandan men: impact of penile circumcision and implications for HIV susceptibilityen_US
dc.typeArticleen_US
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