title: Immune factors influencing the course of infection with Neospora caninum in the murine host.
abstract: This paper investigates the role of specific immune factors on the course of infection in genetic knockout (gko) mice infected with 3 different strains of Neospora caninum. Survival time and parasite persistence were examined in interferon-gamma (IFN-gamma), tumor necrosis factor receptor-2 (TNFR2), interleukin 10 (IL-10), beta 2 microglobulin (beta2M), and inducible nitric oxide synthase (iNOS2) gko or wild-type (wt) mice following infection with either pathogenic (NC-1 or NC-2) or attenuated (NCts-8) N. caninum strains. Infection with NC-1 was 100% lethal in IFN-gamma gko mice, as evidenced by mean survival times of 10-13 days, depending on the challenge dose used. TNFR2 and beta2M gko mice infected with NC-1 or NC-2 strain demonstrated partial susceptibility to disease, as evidenced by histopathology and survival curves. TNFR2 or beta2M gko mice were not susceptible to infection with NCts-8, on the basis of absence of pathology and lack of mortality. Lack of mortality and minimal histopathology scores demonstrated that NC-1, NC-2, and NCts-8 infections were avirulent in IL-10 and iNOS2 gko mice. Adoptive transfer of immune cells from NCts-8 vaccinated normal syngeneic mice into IFN-gamma gko mice significantly (P < 0.05) prolonged mean survival times at all 3 challenge doses of NC-1 but failed to protect against mortality. Interestingly, there was a notable change in the tissue tropism of tachyzoites from the lung and brain in immunocompetent wt, TNFR2 gko, IL-10 gko, beta2M gko, and iNOS2 gko mice to the liver and spleen in IFN-gamma gko mice when challenged with N. caninum. On the basis of these results in gko mice, IFN-gamma is a critical cytokine in the host response against acute neosporosis.
authors.affiliation: Pfizer Global Research and Development, Veterinary Medicine Biologicals, Groton, Connecticut 06340, USA. dianne_m_ritter@groton.pfizer.com
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Ritter
authors.forename: Roy
authors.initials: R
authors.lastname: Kerlin
authors.forename: Gary
authors.initials: G
authors.lastname: Sibert
authors.forename: David
authors.initials: D
authors.lastname: Brake
mesh_terms: D000818:Animals; D001921:Brain / Q000469:parasitology / Q000473:pathology; D003048:Coccidiosis / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006651:Histocytochemistry; D008099:Liver / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018688:Neospora / Q000276:immunology* / Q000472:pathogenicity; D013154:Spleen / Q000469:parasitology / Q000473:pathology; D016019:Survival Analysis
chemical_list: D016207:Cytokines