title: Mice lacking the gene for inducible or endothelial nitric oxide are resistant to sporocyst induced Sarcocystis neurona infections.
abstract: Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. Little is known about the role of immunobiological mediators to this parasite. Nitric oxide (NO) is important in resistance to many intracellular parasites. We, therefore, investigated the role of inducible and endothelial NO in resistance to clinical disease caused by S. neurona in mice. Groups of interferon-gamma gene knockout (IFN-gamma-KO) mice, inducible nitric oxide synthase gene knockout (iNOS-KO) mice, endothelial nitric oxide synthase gene knockout (eNOS-KO) and appropriate genetic background mice (BALB/c or C57BL/6) were orally fed sporocysts or Hanks balanced salt solution. Mice were observed for signs of clinical disease and examined at necropsy. Clinical disease and deaths occurred only in the IFN-gamma-KO mice. Microscopic lesions were seen only in the brains of IFN-gamma-KO mice. Results of this study indicate that iNOS and eNOS are not major mediators of resistance to S. neurona infections. Results of this study suggest that IFN-gamma mediated immunity to S. neurona may be mediated by non-NO-dependent mechanisms.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, 1410 Prices Fork Road, Blacksburg, VA 24061-0342, USA.
authors.forename: Alexa C
authors.initials: AC
authors.lastname: Rosypal
authors.forename: David S
authors.initials: DS
authors.lastname: Lindsay
authors.forename: Robert
authors.initials: R
authors.lastname: Duncan
authors.forename: S Ansar
authors.initials: SA
authors.lastname: Ahmed
authors.forename: Anne M
authors.initials: AM
authors.lastname: Zajac
authors.forename: J P
authors.initials: JP
authors.lastname: Dubey
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D004198:Disease Susceptibility / Q000276:immunology; D004679:Encephalomyelitis / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D005260:Female; D020022:Genetic Predisposition to Disease; D006734:Horse Diseases / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D006736:Horses; D007371:Interferon-gamma / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012522:Sarcocystis / Q000276:immunology / Q000472:pathogenicity*; D012523:Sarcocystosis / Q000235:genetics / Q000276:immunology / Q000662:veterinary*
chemical_list: D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse