Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7

Authors Organisations
  • Natalie Reimers(Author)
    Priority Area Asthma & Allergy, Research Center Borstel (RCB)
  • Arne Homann(Author)
    Priority Area Asthma & Allergy, Research Center Borstel (RCB)
  • Beate Höschler(Author)
    Priority Area Asthma & Allergy, Research Center Borstel (RCB)
  • Kristina Langhans(Author)
    Priority Area Asthma & Allergy, Research Center Borstel (RCB)
  • R. Alan Wilson(Author)
    University of York
  • Christine Pierrot(Author)
    Institut Pasteur de Lille
  • Jamal Khalife(Author)
    Institut Pasteur de Lille
  • Christoph G. Grevelding(Author)
    University of Geissen
  • Iain Chalmers(Author)
  • Maria Yazdanbakhsh(Author)
    Leiden University Medical Center
  • Karl Hoffmann(Author)
  • Cornelis H Hokke(Author)
    Leiden University Medical Center
  • Helmut Haas(Author)
    helminGuard
  • Gabriele Schramm(Author)
    Priority Area Asthma & Allergy, Research Center Borstel (RCB)
Type Article
Original languageEnglish
Article numbere0003593
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number3
DOI
Publication statusPublished - 16 Mar 2015
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Abstract

BACKGROUND: Schistosomiasis is a serious health problem especially in developing countries and affects more than 243 million people. Only few anthelmintic drugs are available up to now. A major obstacle for drug treatment is the different developmental stages and the varying host compartments during worm development. Anthelmintic drugs have been tested mainly on adult schistosomes or freshly transformed cercariae. Knowledge concerning the larval stages is lacking.

METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used in vitro-grown schistosomula (aged between 2 to 14 days) to investigate drug effects of the three anthelmintics praziquantel, artemether, and oxamniquine. Further, we analyzed the antibody accessibility of two exemplary schistosome antigens SmCD59a and SmKK7, before and after drug treatment. Our results demonstrated that praziquantel applied at a concentration of 1 μM inhibited development of all life stages. Application of 10 μM praziquantel led to dramatic morphological changes of all schistosomula. Artemether at 1 and 10 μM had differential effects depending on whether it was applied to 2-day as compared to 7- and 14-day schistosomula. While 2-day schistosomula were not killed but inhibited from further development, severe morphological damage was seen in 7- and 14-day schistosomula. Oxamniquine (1 and 10 μM) led to severe morphological impairment in all life stages. Analyzing the accessibility of the antigens SmCD59a and SmKK7 before drug treatment showed no antibody binding on living intact schistosomula. However, when schistosomula were treated with anthelmintics, both antigens became exposed on the larvae. Oxamniquine turned out to be most effective in promoting antibody binding to all schistosomula stages.

CONCLUSION: This study has revealed marked differences in anthelmintic drug effects against larvae. Drug treatment increases surface antigen presentation and renders larvae accessible to antibody attack.