Schistosoma 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

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.

Schistosoma mansoni infection and socio-behavioural predictors of HIV risk: a cross-sectional study in women from Uganda

“…Consistent with our previous study in men [ 33 ] and despite the socio-behavioral differences observed here, we found that S. mansoni infection was associated with distinct systemic immunological signatures. Specifically, elevated levels of IL-10 and TNF indicate the presence of parasite-driven inflammation in schistosoma-infected women, suggesting that associations with immunological correlates of HIV susceptibility warrant further investigation.…”

Effects of schistosomes on host anti-viral immune response and the acquisition, virulence, and prevention of viral infections: A systematic review

“…By contrast, immune cell populations were not altered in the foreskins of men with S . mansoni infection [ 50 ]. Taken together, these consistently report that schistosome-infected women have genital mucosal alterations in immune cell populations, anti-viral signaling, and HIV viral entry.…”

Schistosomiasis is associated with rectal mucosal inflammation among Kenyan men who have sex with men

“…30 Rectal inflammation is also common in the context of symptomatic S. mansoni disease that presents with GI bleeding or obstruction, 31 and an increased Th17 and Th22 frequency was seen in the blood of asymptomatic S. mansoni -infected Ugandan men. 32 Multiple studies have demonstrated that schistosomiasis can have important effects on systemic (blood) immunology, including the shift from a Th1 to a Th2 immune bias which induces eosinophilia, increased IgE antibodies, and higher levels of the cytokines IL-4 and IL-10. 33 While these systemic changes would not necessarily be expected to enhance HIV risk, quite different immune alterations were seen in the genital mucosa, 7 emphasizing the importance of studying infection impact in different immune compartments.…”