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 Toxoplasma gondii, causes abortion, stillbirths, and congenital neurologic disease in multiple animal species. The present study focuses on the development 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 resistance of inbred strains to N. caninum-induced encephalitis. Relative resistance was defined in terms of central nervous system lesion development and parasite load. Based on other protozoal infections in mice, it was hypothesized that BALB/c and C57BL/6 should be contrasting in their relative resistance to N. caninum, with BALB/c and congenic B10.D2 mice less susceptible than C57BL/6 mice. Contrary to expectation, BALB/c and C57BL/6 were both highly susceptible to the development of N. caninum-induced encephalitis, whereas B10.D2 mice were resistant. Both BALB/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 susceptibility in C57BL/6 and BALB/c mice corresponded with a low splenocyte IFN-gamma: IL-4 ratio. In vivo measurement of Neospora-specific isotype antibodies demonstrated predominately IgG2a in serum from B10.D2 mice and IgG1 in serum from BALB/c and C57BL/6 mice. In conclusion, susceptibility of mice to N. caninum is unique compared to other protozoal diseases. The present study also demonstrates that parasite load is a fundamental measurement for evaluating disease induced by N. caninum and that a type 1 cytokine response may be necessary for regulation of this parameter.
Long
M T
MT
Department of Veterinary Pathology and Microbiology, Washington State University College of Veterinary Medicine, Pullman 99164-7040, USA.
Baszler
T V
TV
Mathison
B A
BA
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001921:Brain / Q000469:parasitology* / Q000473:pathology*; D003048:Coccidiosis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018688:Neospora / Q000254:growth & development / Q000276:immunology
D000913:Antibodies, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma