A Praziquantel Treatment Study of Immune and Transcriptome Profiles in Schistosoma haematobium-Infected Gabonese Schoolchildren. (17th December 2019)

• Record Type: Journal Article
• Authors: Labuda, Lucja A; Adegnika, Ayola A; Rosa, Bruce A; Martin, John; Ateba-Ngoa, Ulysse; Amoah, Abena Serwaa; Lima, Honorine Mbenkep; Meurs, Lynn; Mbow, Moustapha; Manurung, Mikhael D; Zinsou, Jeannot F; Smits, Hermelijn H; Kremsner, Peter G; Mitreva, Makedonka; Yazdanbakhsh, Maria
• Is Part Of: Journal of infectious diseases. Volume 222:Number 12(2020)
• Page Start: 2103
• Page End: 2113
• Publication Date: 2019-12-17
• Subjects: CD4+CD25+FOXP3+ T-cells -- cytokines -- praziquantel -- Schistosoma haematobium; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiz641
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: 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.