Abstract
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 FindingsForeskin 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.
Highlights
HIV continues to be a public health crisis, with 2.3 million new infections and 1.6 million HIV-related deaths in 2013
We hypothesized that S. mansoni infection in the gut mucosa might increase recruitment and activation of HIV target cells at other mucosal sites, and thereby contribute to high HIV rates in fishing communities
We found that men with S. mansoni infection had a greater frequency of HIV target cells in their blood, but not their foreskin tissue, perhaps because foreskin cells did not express mucosal homing markers
Summary
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. Th17 cells in the blood of S. mansoni-infected men demonstrated enhanced function (28.1 vs 16.3% producing multiple cytokines, p = 0.046) These immune alterations were not observed in foreskin tissue. 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. Association of S. mansoni with Increased HIV Target Cells in the Blood support of USAID and other donors; a full list of IAVI donors is available at www.iavi.org The contents of this manuscript are the responsibility of the authors and do not necessarily reflect the views of USAID or the US Government. The common mucosal immune system are not likely to increase HIV susceptibility in the foreskin
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