COMPARISON OF INTRACEREBRAL PARASITE LOAD, LESION DEVELOPMENT, AND SYSTEMIC CYTOKINES IN MOUSE STRAINS INFECTED WITH NEOSPORA-CANINUM

Neospora caninum, an apicomplexan parasite closely related to Toxoplas ma gondii, causes abortion. stillbirths, and congenital neurologic dis ease in multiple animal species. The present study focuses on the deve lopment of encephalitis and intracerebral parasite load that occurs 6 wk postinfection (PI). Utilizing BALB/c. C57BL/6, and B10.D2 mice, an initial investigation was undertaken to determine the relative resista nce of inbred strains to N. caninum-induced encephalitis. Relative res istance was defined in terms of central nervous system lesion dzvelopm mt and parasite load. Based on other protozoal infections in mice. it was hypothesized that BALB/c and C57BL/6 should be contrasting in thei r relative resistance to N. caninum, with BALB/c and congenic B10.D2 m ice less susceptible than C57BL/6 mice. Contrary to expectation, BALB/ c and C57BL/6 were both highly susceptible to the development of N. ca ninum-induced encephalitis, whereas B10.D2 mice were resistant. Both B ALB/c mice and C57BL/6 mice had significantly higher numbers of brain lesions and intracerebral tachyzoites than B10.D2 mice. Resistance in B10.D2 was associated with a high interferon (IFN)-gamma:interleukin ( IL)-4 ratio from antigen-stimulated splenocytes, whereas susceptibilit y in C57BL/6 and BALB/c mice corresponded with a low splenocyte IFN-ga mma:IL-4 ratio. In vivo measurement of Neospora-specific isotype antib odies demonstrated predominately IgG2a in serum from B10.D2 mice and I gG1 in serum from BALB/c and C57BL/6 mice. In conclusion, susceptibili ty of mice to N. caninum is unique compared to other protozoal disease s. The present study also demonstrates that parasite load is a fundame ntal measurement for evaluating disease induced by N. caninum and that a type 1 cytokine response may be necessary for regulation of this pa rameter.