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

J Infect Dis. 2014 Jun 1;209(11):1792-800. doi: 10.1093/infdis/jit826. Epub 2013 Dec 19.

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.

Keywords: Schistosoma mansoni; cytokine; human; immunity; immunopathology; praziquantel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Antigens, Helminth / immunology*
  • Child
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Male
  • Ovum / immunology*
  • Ovum / physiology
  • Praziquantel / therapeutic use
  • Schistosoma mansoni / immunology*
  • Schistosoma mansoni / physiology*
  • Schistosomiasis mansoni / drug therapy
  • Schistosomiasis mansoni / immunology*
  • Schistosomicides / therapeutic use

Substances

  • Antigens, Helminth
  • Cytokines
  • Schistosomicides
  • Praziquantel