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... Show moreBackground. 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. Show less
Meurs, L.; Polderman, A.M.; Melchers, N.V.S.V.; Brienen, E.A.T.; Verweij, J.J.; Groosjohan, B.; ... ; Lieshout, L. van 2017
In Africa, polyparasitism is the rule rather than the exception. The aim of this thesis was to get a detailed insight into the micro-geographical distribution and patterns of S. mansoni and S.... Show moreIn Africa, polyparasitism is the rule rather than the exception. The aim of this thesis was to get a detailed insight into the micro-geographical distribution and patterns of S. mansoni and S. haematobium co-infections, and how this affects host morbidity. A community-wide study was carried out in a co-endemic focus in the north of Senegal, combining epidemiological, ecological, immunological, and geographical analyses. This multidisciplinary approach led to several new insights. Spatial analyses showed significant clustering of Schistosoma infection and morbidity even on a micro scale; S. mansoni and S. haematobium hotspots were found in different sections of one community. Another major finding was that the presence of S. mansoni in co-infections might protect against S. haematobium-specific urinary tract morbidity. Furthermore, it was observed that S. haematobium antigens induced stronger cytokine responses than those of S. mansoni, indicating that the first species may be more immunogenic. The results of this thesis provide new leads for further research on disease etiology and underlying mechanisms in Schistosoma co-infections. Such knowledge is key to rationalizing and optimizing current schistosomiasis control strategies in co-endemic areas and to developing successful elimination strategies in the future. Show less
Meurs, L.; Mbow, M.; Boon, N.; Vereecken, K.; Amoah, A.S.; Labuda, L.A.; ... ; Polman, K. 2014
Background: Schistosoma infection is thought to lead to down-regulation of the host's immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that... Show moreBackground: Schistosoma infection is thought to lead to down-regulation of the host's immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands. Methodology: Peripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zile in Gabon. PBMCs were incubated for 24 h and 72 h with various TLR ligands, as well as schistosomal egg antigen (SEA) and adult worm antigen (AWA). Pro-inflammatory TNF-alpha and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants. Principal Findings: Infected children produced higher adaptive IL-10 responses than uninfected children against schistosomal antigens (72 h incubation). On the other hand, infected children had higher TNF-alpha responses than uninfected children and significantly higher TNF-alpha to IL-10 ratios in response to FSL-1 and Pam3, ligands of TLR2/6 and TLR2/1 respectively. A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation). Conclusions: This pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response. This suggests that S. haematobium infection does not suppress the host's innate immune system in the context of single TLR ligation. Show less
