Optimized dexamethasone immunosuppression enables Echinococcus multilocularis liver establishment after oral egg inoculation in a rat model.
Comparable with immunocompetent humans, rats are considered highly resistant to Echinococcus multilocularis oncosphere invasion, both in nature and after experimental oral inoculation with eggs. Pharmacological immunosuppression with dexamethasone (DMX) was shown to abrogate the resistance of RccHan™:WIST rats, but due to weight losses >20%, many animals had to be excluded from previous experiments. The optimized DXM (Dexafort, MSD Animal Health, Germany) dosage regime presented in this study (each animal: 750 μg DXM at day -13 and 600 μg DXM at day -9 before inoculation) applied subcutaneously to RccHan™:WIST rats, resulted in weight losses ≤20%, but led to liver alveolar echinococcosis (AE) in all eight inoculated animals. Untreated control groups (each n = 8) including RccHan™:WIST (Wistar) and F344/DuCrl (Fischer-344) rats showed no parasite establishment. Antibodies against E. multilocularis metacestode vesicle fluid were present in 7/8 of the infected RccHan™:WIST rats 70 days after inoculation but in none of the control animals. Serology can therefore be used to diagnose AE. This optimized animal model enables a high infection rate in rats and may be applied in future immunological and experimental studies.
Institute of Parasitology, University of Zurich, Winterthurerstrasse 266a, 8057 Zurich, Switzerland.
Deborah Elisabeth
DE
Joekel
Institute of Parasitology, University of Zurich, Winterthurerstrasse 266a, 8057 Zurich, Switzerland. Electronic address: deplazesp@access.uzh.ch.
Peter
P
Deplazes
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004444:Echinococcosis, Hepatic / Q000276:immunology* / Q000469:parasitology; D048210:Echinococcus multilocularis / Q000254:growth & development*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005589:Foxes; D005938:Glucocorticoids / Q000008:administration & dosage; D007121:Immunocompetence; D007074:Immunoglobulin G / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008099:Liver / Q000469:parasitology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar
D000909:Antibodies, Helminth; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D003907:Dexamethasone
Alveolar echinococcosis; Animal model; Fischer-344 rats; Immunosuppression; Oncosphere invasion; Resistance; Wistar rat