title: Drug-induced exposure of Schistosoma mansoni antigens SmCD59a and SmKK7.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cellular Allergology, Priority Area Asthma & Allergy, Research Center Borstel (RCB), Borstel, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Reimers
authors.affiliation: Division of Cellular Allergology, Priority Area Asthma & Allergy, Research Center Borstel (RCB), Borstel, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Homann
authors.affiliation: Division of Cellular Allergology, Priority Area Asthma & Allergy, Research Center Borstel (RCB), Borstel, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Höschler
authors.affiliation: Division of Cellular Allergology, Priority Area Asthma & Allergy, Research Center Borstel (RCB), Borstel, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Langhans
authors.affiliation: Centre for Immunology and Infection, Department of Biology, University of York, York, United Kingdom.
authors.forename: R Alan
authors.initials: RA
authors.lastname: Wilson
authors.affiliation: Center for Infection and Immunity of Lille, Inserm U1019, CNRS 8204, Institut Pasteur de Lille, Lille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Pierrot
authors.affiliation: Center for Infection and Immunity of Lille, Inserm U1019, CNRS 8204, Institut Pasteur de Lille, Lille, France.
authors.forename: Jamal
authors.initials: J
authors.lastname: Khalife
authors.affiliation: Institute for Parasitology, University of Giessen, Giessen, Germany.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Grevelding
authors.affiliation: Institute of Biological, Environmental & Rural Sciences (IBERS), Aberystwyth University, Aberystwyth, United Kingdom.
authors.forename: Iain W
authors.initials: IW
authors.lastname: Chalmers
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.affiliation: Institute of Biological, Environmental & Rural Sciences (IBERS), Aberystwyth University, Aberystwyth, United Kingdom.
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hoffmann
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
authors.affiliation: Division of Cellular Allergology, Priority Area Asthma & Allergy, Research Center Borstel (RCB), Borstel, Germany; helminGuard, Suelfeld, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Haas
authors.affiliation: Division of Cellular Allergology, Priority Area Asthma & Allergy, Research Center Borstel (RCB), Borstel, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schramm
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D000947:Antigens, Helminth / Q000032:analysis*; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology; D018957:CD59 Antigens / Q000032:analysis*; D006801:Humans; D008297:Male; D011223:Praziquantel / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000276:immunology
chemical_list: D000871:Anthelmintics; D000947:Antigens, Helminth; D037621:Artemisinins; D018957:CD59 Antigens; D011223:Praziquantel; D000077549:Artemether