Infection of Immunodeficient Horses withSarcocystis neuronaDoes Not Result in Neurologic Disease

Abstract

Equine protozoal myeloencephalitis (EPM) is one of the most common neurologic disorders of horses in the Americas. Although there are occasional reports of neurologic disease in horses due to Neospora hughesii, EPM is most frequently associated with infection with the apicomplexan parasite Sarcocystis neurona (9). Despite recent advances in our understanding of the life cycle of S. neurona (1, 2, 10), very little is known about the pathogenesis of infection in horses (9). S. neurona can parasitize all regions of the equine central nervous system (CNS). The route of migration of the parasite from the time of ingestion of sporocysts to neuroinvasion is unknown. Studies of gamma interferon (IFN-␥) knockout (GKO) mice, which develop fulminant neurologic disease after infection, suggest that S. neurona may initially multiply in visceral tissues (6, 8).The major goal of our laboratory is to investigate the pathogenesis of S. neurona infection in horses by determining steps in the progression of infection and the role of innate and adaptive immunity in the control of infection and neuropathology. GKO mice develop profound neurologic disease when they are infected with S. neurona (6,8), suggesting that IFN-␥ is crucial in the elimination of that infection in mice. IFN-␥ is produced by lymphocytes during an adaptive Th1 immune response, and adaptive immune responses are presumed to be important in the protection of horses from S. neurona. However, in the absence of adaptive immune responses, mice are protected from Toxoplasma gondii infection, presumably through the production of IFN-␥ by cells of the innate immune system (5, 13). Similarly, two mice with severe combined immune deficiency (SCID) experimentally infected with S. neurona did not develop neurologic disease (18). In a preliminary experiment, we infected an Arabian horse with SCID (19, 28) with sporocysts of S. neurona. The infected horse became parasitemic, and S. neurona merozoites were isolated from the blood on postinfection day (PID) 21 (16). This isolate was designated the WSU-1 strain of S. neurona. Although this SCID horse did not exhibit convincing neurologic deficits, S. neurona DNA was detectable by PCR after long-term culture of brain tissue obtained at necropsy.In the present study, we further investigate the pathogenesis of S. neurona infection in SCID and immunocompetent (IC) horses. Horses were infected orally with sporocysts isolated from the feces of opossums or intravenously (i.v.) with merozoites of the WSU-1 strain of S. neurona. Parasitemia was monitored after infection by collection of blood samples for culture and PCR. Horses were monitored for the development of neurologic abnormalities. At the time of necropsy, tissues were collected for culture, PCR, immunohistochemistry (IHC), and histopathology to determine the presence of S. neurona and associated inflammatory lesions in peripheral tissues or the CNS. MATERIALS AND METHODSExperimental animals. All horses were obtained from the Arabian herd at Washington State College of Veterinary...

Polyphasic Rhabdomyositis in California Sea Lions (Zalophus Californianus): Pathology and Potential Causes

“…6 Further evidence of the role of the immune response in the pathogenesis of S. neurona tissue damage is the fact that in horses lacking T and B lymphocytes (foals with severe combined immunodeficiency), S. neurona experimental inoculation does not cause clinical disease. 20,32 In addition, in equine protozoal meningoencephalitis, other factors such as stress and young age have been indicated as risk factors for the presentation of disease. 26,29 In the case of CSLs, the effect of stress is not clear but likely to play a role given the fact that many CSLs with significant rhabdomyositis and moderate S. neurona titers had significant comorbidities, such as urogenital carcinoma and domoic acid toxicosis, conditions that are likely to cause significant stress.…”

Equine Protozoal Myeloencephalitis

“…Paradoxically, severe combined immunodeficient mice and horses, which completely lack adaptive immune systems but have a population of natural killer cells, do not get neurologic disease when infected with S neurona, despite persistent, low-level infection. 55,57,58 Initial work aimed at reproducing EPM in horses used as challenge inoculum a mixture of uncharacterized sporocysts collected from 10 feral opossums. 59 When molecular markers were identified that were able to differentiate the various Sarcocystis spp sporocysts found in opossums, 60 it became possible to use challenge inocula containing known quantities of S neurona sporocysts.…”

Seroprevalencia de Sarcocystis neurona en caballos de Montería (Córdoba, Colombia)

“…. La ruta de migración por la ingestión de esporocistos a neuroinvasión es desconocido, pero se han evidenciado parásitos en el SNC en equinos, que han desarrollado enfermedad neurológica, después de una inoculación experimental(Sellon et al 2004).…”