Immune Responses Induced by Repeated Treatment Do Not Result in Protective Immunity to<i>Schistosoma haematobium:</i>Interleukin (IL)–5 and IL‐10 Responses

Biggelaar, Anita H. J. van den; Borrmann, Steffen; Kremsner, Peter G.; Yazdanbakhsh, Maria

doi:10.1086/344352

Cited by 44 publications

(34 citation statements)

References 41 publications

(45 reference statements)

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“…This reliance on exposure to antigen is indicated by multiple treatments, and consequently multiple exposures to antigen, resulting in greater IL-5 and IL-13 production than a single treatment [15]. In the current study, the correlation between the increase in the type 2 cytokine levels to SWA and pretreatment infection intensities suggests that antigen dose upon treatment is crucial to this increase.…”

Section: Discussionmentioning

confidence: 64%

“…Treatment causes schistosome worms to disintegrate, exposing the host to these same sequestered adult worm antigens [31], and the other hypothesis for posttreatment increases in type 2 cytokines in response to SWA stimulation is boosting of the recall response via in vivo exposure to antigens [15, 16]. This reliance on exposure to antigen is indicated by multiple treatments, and consequently multiple exposures to antigen, resulting in greater IL-5 and IL-13 production than a single treatment [15].…”

Section: Discussionmentioning

confidence: 99%

“…Treatment of schistosomiasis increases T-cell proliferation after SWA stimulation, suggesting that T cells may also be SWA hyporesponsive [3, 14]. However, it has also been proposed that exposure to previously cryptic antigens in the worm, upon treatment with praziquantel, boosts SWA-specific type 2 cytokine responses [15, 16]. …”

mentioning

confidence: 99%

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Posttreatment Changes in Cytokines Induced by Schistosoma mansoni Egg and Worm Antigens: Dissociation of Immunity- and Morbidity-Associated Type 2 Responses

Wilson

Jones

Kenty

et al. 2013

The Journal of Infectious Diseases

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Background. Human type 2 cytokine responsiveness to schistosome antigens increases after treatment; due either to removal of the immunosuppressive effects of active infection or immunological boosting by antigens released from dying parasites. We determined the responsiveness to Schistosoma mansoni over a 2-year period, when reinfection was restricted by interrupting transmission.Methods. The proinflammatory and type 2 responses of Kenyan schoolchildren were measured before, and 1 year and 2 years posttreatment in whole blood cultures stimulated with soluble egg antigen (SEA) or soluble worm antigen (SWA). The site of S. mansoni transmission was molluscicided throughout.Results. Pretreatment proinflammatory responses to SEA were high but reduced 1 and 2 years posttreatment, whereas type 2 responses were low pretreatment and increased 1 and 2 years posttreatment. Type 2 responses to SWA were high pretreatment and increased at 1 year, with no further increases at 2 years posttreatment. Children infected at follow-up had lower SEA, but not SWA, posttreatment type 2 responsiveness. Increases at 1 year in type 2 SWA, but not SEA, responsiveness correlated with pretreatment egg counts.Conclusions. Removal of immunosuppressive effects of active infection increases SEA type 2 responsiveness; long-term SWA type 2 responsiveness is due to treatment-induced immunological boosting. Dissociation of type 2 responses potentially protects against severe egg-associated immunopathology during infection, while allowing worm-antigen derived immunity to develop.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

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Posttreatment Changes in Cytokines Induced by Schistosoma mansoni Egg and Worm Antigens: Dissociation of Immunity- and Morbidity-Associated Type 2 Responses

Wilson

Jones

Kenty

et al. 2013

The Journal of Infectious Diseases

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“…An interesting finding was a negative standardized mean difference observed in the association between IgE levels and reinfection with schistosomes (Figure 5 and Figure S2) inferred from meta-analysis on 8 studies [23], [31], [39], [44], [48]–[51]. However, subgroup analyses of these associations with IgE levels against adult worm antigen (SWA) (Figure 5A) and egg antigen (SEA) (Figure 5B) were not statistically significant (For anti-SWA IgE, SMD = −0.06, 95% CI = −0.59–0.46, Z = 0.23, p = 0.82; for anti-SEA IgE, SMD = −0.03, 95% CI = −0.38–0.32, Z = 0.15, p = 0.88).…”

Section: Resultsmentioning

confidence: 93%

Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

et al. 2014

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BackgroundSchistosomiasis is still a major public health burden in the tropics and subtropics. Although there is an effective chemotherapy (Praziquantel) for this disease, reinfection occurs rapidly after mass drug administration (MDA). Because the entire population do not get reinfected at the same rate, it is possible that host factors may play a dominant role in determining resistance or susceptibility to reinfection with schistosomes. Here, we systematically reviewed and meta-analyzed studies that reported associations between reinfection with the principal human-infecting species (S. mansoni, S. japonicum and S. haematobium) and host socio-demographic, epidemiological, immunological and genetic factors.Methodology/Principal FindingsPubMed, Scopus, Google Scholar, Cochrane Review Library and African Journals Online public databases were searched in October 2013 to retrieve studies assessing association of host factors with reinfection with schistosomes. Meta-analysis was performed to generate pooled odds ratios and standardized mean differences as overall effect estimates for dichotomous and continuous variables, respectively. Quality assessment of included studies, heterogeneity between studies and publication bias were also assessed. Out of the initial 2739 records, 109 studies were included in the analyses, of which only 32 studies with 37 data sets were eligible for quantitative data synthesis. Among several host factors identified, strong positive association was found with age and pre-treatment intensity, and only slightly for gender. These factors are major determinants of exposure and disease transmission. Significant positive association was found with anti-SWA IgG4 level, and a negative overall effect for association with IgE levels. This reconfirmed the concept that IgE/IgG4 balance is a major determinant of protective immunity against schistosomiasis. Other identified determinants were reported by a small number of studies to enable interpretation.ConclusionsOur data contribute to the understanding of host-parasite interaction as it affects reinfection, and is a potential tool to guide planning and tailoring of community interventions to target high-risk groups.

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“…There is also mounting evidence that PZQ boosts both innate and adaptive immune responses to schistosome antigens [8]–[10] due to increased worm death in the bloodstream and an associated increase in exposure of schistosome antigens to immune recognition after treatment [11], [12]. However, although there is some evidence that this immunological boost promotes a degree of resistance to re-infection in humans [10], [13], both infection prevalence and associated pathologies return after treatment and therefore repeated treatment is required [14], [15]. For nearly 30 years an anti-schistosome vaccine has been seen as a desirable long-term adjunct to drug treatment [3], [16].…”

Section: Introductionmentioning

confidence: 99%

Cytokine Responses to the Anti-schistosome Vaccine Candidate Antigen Glutathione-S-transferase Vary with Host Age and Are Boosted by Praziquantel Treatment

et al. 2014

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BackgroundImproved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ), which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST) is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment.MethodologyBlood samples from inhabitants of a Schistosoma haematobium-endemic area were incubated for 48 hours with or without GST before (n = 195) and six weeks after PZQ treatment (n = 107). Concentrations of cytokines associated with innate inflammatory (TNFα, IL-6, IL-8), type 1 (Th1; IFNγ, IL-2, IL-12p70), type 2 (IL-4, IL-5, IL-13), type 17 (IL-17A, IL-21, IL-23p19) and regulatory (IL-10) responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA). Factor analysis and multidimensional scaling were used to analyse multiple cytokines simultaneously.Principal FindingsA combination of GST-specific type 2 (IL-5 and IL-13) and regulatory (IL-10) cytokines was significantly lower in 10–12 year olds, the age group at which S. haematobium infection intensity and prevalence peak, than in 4–9 or 13+ year olds. Following PZQ treatment there was an increase in the number of participants producing detectable levels of GST-specific cytokines (TNFα, IL-6, IL-8, IFNγ, IL-12p70, IL-13 and IL-23p19) and also a shift in the GST-specific cytokine response towards a more pro-inflammatory phenotype than that observed before treatment. Participant age and pre-treatment infection status significantly influenced post-treatment cytokine profiles.Conclusions/SignificanceIn areas where schistosomiasis is endemic host age, schistosome infection status and PZQ treatment affect the cellular cytokine response to GST. Thus the efficacy of a GST-based vaccine may also be shaped by the demographic and epidemiological characteristics of targeted populations.

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Immune Responses Induced by Repeated Treatment Do Not Result in Protective Immunity toSchistosoma haematobium:Interleukin (IL)–5 and IL‐10 Responses

Cited by 44 publications

References 41 publications

Posttreatment Changes in Cytokines Induced by Schistosoma mansoni Egg and Worm Antigens: Dissociation of Immunity- and Morbidity-Associated Type 2 Responses

Posttreatment Changes in Cytokines Induced by Schistosoma mansoni Egg and Worm Antigens: Dissociation of Immunity- and Morbidity-Associated Type 2 Responses

Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

Cytokine Responses to the Anti-schistosome Vaccine Candidate Antigen Glutathione-S-transferase Vary with Host Age and Are Boosted by Praziquantel Treatment

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