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Background: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.Methods: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.Results: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were negatively associated with CD4+CD25+FOXP3+ T-cells and accompanied by increased frequency of effector memory T-cells. Innate responses to Toll like receptor (TLR) ligation decreased with treatment and showed positive association with CD4+CD25+FOXP3+ T-cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, whereas parasite removal was associated with a more quiescent profile. Further analysis indicated that alteration in cellular energy metabolism was associated with S haematobium infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), transcription factors that negatively regulate T-cell activation, may play a role in adaptive immune hyporesponsiveness.Conclusions: Using a longitudinal study design, we found contrasting effects of schistosome infection on innate and adaptive immune responses. Whereas the innate immune system appears more activated, the adaptive immunity is in a hyporesponsive state reflected in alterations in CD4+CD25+FOXP3+ T-cells, cellular metabolism, and transcription factors involved in anergy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic schistosome infections are associated with T-cell hyporesponsiveness and a strong regulatory network. Murine studies have shown that schistosome infections can induce regulatory CD1d(hi) B cells, which inhibit inflammatory responses. Here, we evaluated the influence of regulatory B cells (Bregs) on T-cell cytokines in vitro in human schistosomiasis. METHODS: Gabonese young adults were recruited from areas where Schistosoma haematobium (S.h) infections were high or low endemic. The study participants were categorized as infected or uninfected from an high endemic area or uninfected from a low endemic (nonendemic) area. Their B cells were studied for Breg subset markers and cocultured with allogenic anti-CD3-stimulated CD4(+) T cells, followed by T-cell cytokine analysis. RESULTS: A greater percentage of B cells from S. haematobium-infected donors expressed cytoplasmic interleukin 10 (IL-10) and membrane-bound latency-associated peptide/transforming growth factor [beta]1, compared with uninfected donors. T cells produced less interferon [gamma], interleukin 4, and interleukin 17 upon coculture with B cells from schistosome-infected individuals only, while the conversion to CD25(hi)FoxP3(+) and the percentage of IL-10(+) T cells was enhanced. Interestingly, depletion of the prominent IL-10-producing B-cell subset, CD1d(hi) cells, resulted in less IL-10(+) T cells in the S. haematobium-infected group, while levels of FoxP3(+) regulatory T cells remained unaffected. CONCLUSIONS: Schistosomes can induce functional Bregs in humans that may be instrumental in general T-cell hyporesponsiveness and may contribute to the increased regulatory milieu found in schistosomiasis. [ABSTRACT FROM AUTHOR]