Susceptibility of B-cell deficient C57BL/6 (μMT) mice to Neospora caninum infection

Neospora caninum is a coccidian parasite of veterinary importance by causing abortion or stillbirth in cattle among other problems in diverse animal species. We assessed an experimental murine model for its suitability to study the immune response to N. caninum infection. Thus, wild-type (wt) C57BL/6 mice and B-cell land consequently antibody)deficient mu MT mice were infected with N. caninum tachyzoites and sacrificed at days 10, 24 and 29-44 post infection (dpi). Various organs were collected for parasitological and pathological analysis, spleen and serum for immunological investigations. Splenocytes were in vitro-stimulated with N. caninum (NC)- and T. gondii-antigens for assessing T cell proliferation and cytokine production. While wt mice were resistant to disease, mu MT mice died starting from 29dpi onwards. Histological examination of brain tissue from mu MT mice exhibited a high infection intensity with multifocal necrotic cerebral lesions, which were absent in the brains of wt mice. NC antigen-stimulated spleen cells of both wt and mu MT mice infected with N. caninum showed a marked proliferative depression at I0dpi. At 24dpi, this immunosuppression was still maintained in mu MT mice whereas it was restored in wt mice. Stimulated splenocytes of infected mu MT mice secreted significantly less IFN-gamma and less IL-10 than corresponding wt splenocytes. For IL-10, this difference increased with time. The susceptibility of mu MT mice appeared associated to B-cell deficiency, allowing the persistant spr ead of the parasite causing immunosuppression and finally resulting in a lethal outcome of infection.