Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 222, Issue 12, Pages 2103-2113Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz641
Keywords
CD4(+)CD25(+)FOXP3(+) T-cells; cytokines; praziquantel; Schistosoma haematobium; transcriptome profiling
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Funding
- European Union (EU) [INCO-CT-2006-032405]
- EU-funded project the Immunological Interplay between Poverty Related Diseases and Helminth Infections: An African-European Research Initiative IDEA [HEALTH-F3-2009-241642]
- Deutsche Forschungsgemeinschaft-funded project Deutsch-Afrikanische Kooperationsprojekte in der Infektiologie (DFG) [KR 1150/6-1]
- National Institutes of Health National Institute of Allergy and Infectious Diseases [AI081803]
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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.
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