The role of B- and T-cell immunity in toltrazuril-treated C57BL/6 WT, microMT and nude mice experimentally infected with Neospora caninum.
Neospora caninum is a protozoan parasite predominantly known for causing abortion in cattle and neuromuscular disease in dogs. So far, no efficient metaphylactic chemotherapy has been developed. In preliminary studies, toltrazuril had been successfully used against experimental neosporosis in mice and calves. In the present study, we used immunocompetent and immunodeficient mouse strains to address the role of immunity in supporting the chemotherapy of experimental N. caninum infection. WT, microMT and athymic nude mice were intraperitoneally inoculated with 1x10(6) Nc-1 tachyzoites. The drug was administered in the drinking water for 6 consecutive days so as to obtain a daily dose of approximately 20 mg toltrazuril/kg body weight. The course of infection was monitored by clinical, histological and immunohistochemical means, as well as by the search for parasite DNA using PCR-analyses of various organs. In immunocompetent WT mice, treatment proved to be of high efficacy by abrogation of any lesion formation or PCR-positivity in medicated C57BL/6 mice and a significant reduction of lesion formation or PCR-positivity in BALB/c animals. Similarly, treated microMT mice exhibited a significant reduction in cerebral lesion formation as well as in parasite DNA detectability by PCR when compared to untreated animals. Athymic nude mice, however, did not respond to treatment in that only a delay of the parasite dissemination was achieved, and nude mice still showed the neosporosis disease symptoms, although later than untreated animals. We conclude that treatment with toltrazuril appears to act parasitostatically rather than parasitocidically. This is supported by the fact that: (1) although the lack of B-cells did not impair the effect of toltrazuril, (2) the lack of T-cells did not allow for a full efficacy of treatment. Therefore, chemotherapy with toltrazuril against experimental infections with N. caninum requires the support of T-cell immunity in order to be successful.
Institute of Parasitology, University of Berne, Länggass-Strasse 122, 3012 Berne, Switzerland.
Petra
P
Ammann
Andreas
A
Waldvogel
Isabel
I
Breyer
Marco
M
Esposito
Norbert
N
Müller
Bruno
B
Gottstein
D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D001921:Brain / Q000469:parasitology / Q000473:pathology; D003048:Coccidiosis / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D006321:Heart / Q000469:parasitology; D007150:Immunohistochemistry; D007668:Kidney / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D008168:Lung / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018688:Neospora / Q000276:immunology* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology*; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000981:Antiprotozoal Agents; D014227:Triazines; C036670:toltrazuril