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

Longitudinal cytokine production in whole blood cultures stimulated with Schistosoma mansoni soluble egg antigen (SEA). Shown are the levels of cytokines and the chemokine CCL5 measured in whole blood cultures stimulated with SEA pretreatment, 1 year posttreatment, and 2 years posttreatment. Nonsignificant (ns) comparisons using paired Wilcoxon tests are indicated. All other longitudinal comparisons remained significant after correction for multiple testing by Simes-modified Bonferroni method. Abbreviations: IFN-γ, interferon gamma; IL, interleukin; TNF-α, tumor necrosis factor alpha.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

JIT826F3: Longitudinal cytokine production in whole blood cultures stimulated with Schistosoma mansoni soluble egg antigen (SEA). Shown are the levels of cytokines and the chemokine CCL5 measured in whole blood cultures stimulated with SEA pretreatment, 1 year posttreatment, and 2 years posttreatment. Nonsignificant (ns) comparisons using paired Wilcoxon tests are indicated. All other longitudinal comparisons remained significant after correction for multiple testing by Simes-modified Bonferroni method. Abbreviations: IFN-γ, interferon gamma; IL, interleukin; TNF-α, tumor necrosis factor alpha.

Mentions: IL-1β, IL-12p40, TNF-α, CCL5, and IL-6 responses all significantly decreased in SEA-stimulated cultures 1 year posttreatment in comparison with pretreatment cultures (Figure 3). These responses in 2 years posttreatment SEA-stimulated cultures were significantly lower again compared with 1 year posttreatment, except for IL-1β (U = 1187, P = .281). In contrast, IFN-γ responses in SEA-stimulated cultures were significantly higher 1 year posttreatment in comparison with pretreatment, but at 2 years posttreatment were lower than both pretreatment and 1 year posttreatment. IL-10 responses in SEA-stimulated cultures were not significantly lower 1 year posttreatment compared to pretreatment (U = 1386, P = .443), but were significantly lower 2 years posttreatment than at 1 year posttreatment.Figure 3.


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)

Longitudinal cytokine production in whole blood cultures stimulated with Schistosoma mansoni soluble egg antigen (SEA). Shown are the levels of cytokines and the chemokine CCL5 measured in whole blood cultures stimulated with SEA pretreatment, 1 year posttreatment, and 2 years posttreatment. Nonsignificant (ns) comparisons using paired Wilcoxon tests are indicated. All other longitudinal comparisons remained significant after correction for multiple testing by Simes-modified Bonferroni method. Abbreviations: IFN-γ, interferon gamma; IL, interleukin; TNF-α, tumor necrosis factor alpha.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

JIT826F3: Longitudinal cytokine production in whole blood cultures stimulated with Schistosoma mansoni soluble egg antigen (SEA). Shown are the levels of cytokines and the chemokine CCL5 measured in whole blood cultures stimulated with SEA pretreatment, 1 year posttreatment, and 2 years posttreatment. Nonsignificant (ns) comparisons using paired Wilcoxon tests are indicated. All other longitudinal comparisons remained significant after correction for multiple testing by Simes-modified Bonferroni method. Abbreviations: IFN-γ, interferon gamma; IL, interleukin; TNF-α, tumor necrosis factor alpha.
Mentions: IL-1β, IL-12p40, TNF-α, CCL5, and IL-6 responses all significantly decreased in SEA-stimulated cultures 1 year posttreatment in comparison with pretreatment cultures (Figure 3). These responses in 2 years posttreatment SEA-stimulated cultures were significantly lower again compared with 1 year posttreatment, except for IL-1β (U = 1187, P = .281). In contrast, IFN-γ responses in SEA-stimulated cultures were significantly higher 1 year posttreatment in comparison with pretreatment, but at 2 years posttreatment were lower than both pretreatment and 1 year posttreatment. IL-10 responses in SEA-stimulated cultures were not significantly lower 1 year posttreatment compared to pretreatment (U = 1386, P = .443), but were significantly lower 2 years posttreatment than at 1 year posttreatment.Figure 3.

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