Resistance induced by drug abbreviated Schistosoma mansoni infections: treatment with the drug Ro11-3128 leads to enhanced antigen presentation.
Treatment of mice with the benzodiazepine derivative Ro11-3128 1-2 days post-infection with Schistosoma mansoni leads to arrest of virtually all schistosomula at the skin stage, and results in the development of protective immunity to challenge infection. A characteristic feature of Ro11-3128 treatment in vitro is the formation of exudates and membranous blebs at the schistosomular surface; other drugs tested, such as Ro15-5458 and oxamniquine which are also effective against the skin stages but relatively ineffective in inducing protection, do not induce this reaction. Here, we have examined whether such in vitro treatment causes enhanced presentation of schistosomular antigens by host antigen-presenting cells (APC) using an in vitro assay with activated peritoneal adherent cells as APC and T cells from S. mansoni antigen-sensitized mice. We have shown that viable mechanically transformed schistosomula (MS) can be processed and presented with similar kinetics to soluble antigen. However, in vitro drug treatment leads to enhanced presentation of MS. Experiments in which membranous blebs and antigen released by Ro11-3128-treated parasites during in vitro culture were separated from the remaining intact schistosomula, demonstrated significant stimulatory activity in the soluble and particulate-released antigen fractions. Filtration, antigen transfer experiments and SDS-PAGE analysis of the released material further suggested that most of the activity resided in the particulate fraction. Thus, quantitative and qualitative changes to antigen presentation by Ro11-3128 treatment early after infection may underlie the immunoprotective efficacy of Ro11-3128-abbreviated infections.
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, UK.
D A
DA
Smith
Q D
QD
Bickle
P M
PM
Kaye
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology; D001570:Benzodiazepinones / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media; D004306:Dose-Response Relationship, Immunologic; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000276:immunology; D012556:Schistosomicides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D002998:Clonazepam / Q000031:analogs & derivatives
D000947:Antigens, Helminth; D001570:Benzodiazepinones; D003470:Culture Media; D012556:Schistosomicides; C020602:meclonazepam; D002998:Clonazepam