Limits...
Posttreatment changes in cytokines induced by Schistosoma mansoni egg and worm antigens: dissociation of immunity- and morbidity-associated type 2 responses.

Wilson S, Jones FM, Kenty LC, Mwatha JK, Kimani G, Kariuki HC, Dunne DW - J. Infect. Dis. (2013)

Bottom Line: 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.Increases at 1 year in type 2 SWA, but not SEA, responsiveness correlated with pretreatment egg counts.Dissociation of type 2 responses potentially protects against severe egg-associated immunopathology during infection, while allowing worm-antigen derived immunity to develop.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Cambridge, United Kingdom.

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

Cohort recruitment and follow-up. Shown is the treatment efficacy at 5 weeks, and the success of follow-up and prevalence (P) of Schistosoma mansoni at 1 year and 2 years posttreatment. aThree individuals successfully followed up at 1 and 2 years posttreatment did not provide stool samples at 5 weeks. bPrevalence based on 39 individuals and c30 individuals, due to missing parasitological data among those followed up immunologically at 2 years posttreatment.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4017363&req=5

JIT826F1: Cohort recruitment and follow-up. Shown is the treatment efficacy at 5 weeks, and the success of follow-up and prevalence (P) of Schistosoma mansoni at 1 year and 2 years posttreatment. aThree individuals successfully followed up at 1 and 2 years posttreatment did not provide stool samples at 5 weeks. bPrevalence based on 39 individuals and c30 individuals, due to missing parasitological data among those followed up immunologically at 2 years posttreatment.

Mentions: Ninety-one Akamba schoolchildren, 43 boys and 48 girls, aged 7–18 years (mean, 11.95 years), attending Mbeetwani Primary School, Makueni District, Kenya, participated in the study (Figure 1). Children were selected on the basis of presentation with hepatomegaly at baseline, to assess regression of morbidity and corresponding immunological measurements. None had ultrasound-detectable periportal fibrosis [18]. Three stool samples were collected from each participant and 2 Kato-Katz slides were prepared from each stool for S. mansoni egg counts. All participants were treated with 40 mg/kg praziquantel after samples were collected. Three stools were collected at 5 weeks posttreatment from 83 participants to assess efficacy of treatment.Figure 1.


Posttreatment changes in cytokines induced by Schistosoma mansoni egg and worm antigens: dissociation of immunity- and morbidity-associated type 2 responses.

Wilson S, Jones FM, Kenty LC, Mwatha JK, Kimani G, Kariuki HC, Dunne DW - J. Infect. Dis. (2013)

Cohort recruitment and follow-up. Shown is the treatment efficacy at 5 weeks, and the success of follow-up and prevalence (P) of Schistosoma mansoni at 1 year and 2 years posttreatment. aThree individuals successfully followed up at 1 and 2 years posttreatment did not provide stool samples at 5 weeks. bPrevalence based on 39 individuals and c30 individuals, due to missing parasitological data among those followed up immunologically at 2 years posttreatment.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017363&req=5

JIT826F1: Cohort recruitment and follow-up. Shown is the treatment efficacy at 5 weeks, and the success of follow-up and prevalence (P) of Schistosoma mansoni at 1 year and 2 years posttreatment. aThree individuals successfully followed up at 1 and 2 years posttreatment did not provide stool samples at 5 weeks. bPrevalence based on 39 individuals and c30 individuals, due to missing parasitological data among those followed up immunologically at 2 years posttreatment.
Mentions: Ninety-one Akamba schoolchildren, 43 boys and 48 girls, aged 7–18 years (mean, 11.95 years), attending Mbeetwani Primary School, Makueni District, Kenya, participated in the study (Figure 1). Children were selected on the basis of presentation with hepatomegaly at baseline, to assess regression of morbidity and corresponding immunological measurements. None had ultrasound-detectable periportal fibrosis [18]. Three stool samples were collected from each participant and 2 Kato-Katz slides were prepared from each stool for S. mansoni egg counts. All participants were treated with 40 mg/kg praziquantel after samples were collected. Three stools were collected at 5 weeks posttreatment from 83 participants to assess efficacy of treatment.Figure 1.

Bottom Line: 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.Increases at 1 year in type 2 SWA, but not SEA, responsiveness correlated with pretreatment egg counts.Dissociation of type 2 responses potentially protects against severe egg-associated immunopathology during infection, while allowing worm-antigen derived immunity to develop.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Cambridge, United Kingdom.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus