02694nas a2200313 4500000000100000008004100001653001900042653002400061653001500085653000800100653001800108100001500126700001700141700001500158700001500173700001400188700001300202700001500215700001400230700001400244700001500258700001100273245017800284856007900462300001300541490000600554520180600560022001402366 2015 d10aT helper cells10aSchistosoma mansoni10aImmunology10aHIV10aCo-infections1 aProdger JL1 aSsemaganda A1 aSsetaala A1 aKitandwe P1 aMuyanja E1 aMpendo J1 aNanvubya A1 aWambuzi M1 aNielsen L1 aKiwanuka N1 aKaul R00aSchistosoma mansoni infection in Ugandan men is associated with increased abundance and function of HIV target cells in blood, but not the foreskin: A cross-sectional study. uhttp://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004067  ae00040670 v93 a

BACKGROUND: Schistosoma mansoni infection has been associated with an increased HIV prevalence in humans and SHIV incidence in primate models. We hypothesized that immune activation from this gastrointestinal mucosa infection would increase highly HIV-susceptible CD4 T cell subsets in the blood and the foreskin through common mucosal homing.

METHODOLOGY/PRINCIPAL FINDINGS: Foreskin tissue and blood were obtained from 34 HIV- and malaria-uninfected Ugandan men who volunteered for elective circumcision, 12 of whom were definitively positive for S. mansoni eggs in stool and 12 definitively negative for both S. mansoni eggs and worm antigen. Tissue and blood T cell subsets were characterized by flow cytometry and immunohistochemistry (IHC). Th17 and Th1 cells from both the blood and foreskin expressed higher levels of CCR5 and were more activated than other CD4 T cell subsets. S. mansoni-infected men had a higher frequency of systemic Th1 cells (22.9 vs. 16.5% of blood CD4 T cells, p<0.05), Th17 cells (2.3 vs. 1.5%, p<0.05), and Th22 cells (0.5 vs. 0.3%, p<0.01) than uninfected men. Additionally, Th17 cells in the blood of S. mansoni-infected men demonstrated enhanced function (28.1 vs. 16.3% producing multiple cytokines, p = 0.046). However, these immune alterations were not observed in foreskin tissue.

CONCLUSIONS/SIGNIFICANCE: S. mansoni infection was associated with an increased frequency of highly HIV-susceptible Th1, Th17 and Th22 cell subsets in the blood, but these T cell immune differences did not extend to the foreskin. S. mansoni induced changes in T cell immunology mediated through the common mucosal immune system are not likely to increase HIV susceptibility in the foreskin.

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