|Knowles, Donald - Don|
Submitted to: Journal of Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/15/2003
Publication Date: 8/1/2004
Citation: Sellon, D.C., Knowles Jr, D.P., Greiner, E.C., Long, M.T., Hines, M.T., Hochstatter, T., Hasel, K.M., Ueti, M., Gillis, K., Dame, J.B. 2004. Depletion of natural killer cells does not result in neurologic disease due to sarcocystis neurona in mice with severe combined immunodeficiency. Journal of Parasitology. 90(4):782-788. Interpretive Summary: Sarcocystis neurona is a complex parasite which causes equine protozoal myeloencephalitis, an inflammatory disease of the equine spinal cord. Immune mechanisms which control this parasite and prevent inflammation are not known. These data show that IFN-gamma mediates protection from neurologic disease causes by S. neurona within SCID mice. Depletion of NK cells from SCID mice did not result in neurologic disease indicating an alternate source of IFN-gamma.
Technical Abstract: Sarcocystis neurona is an apicomplexan parasite that is the primary etiologic agent of equine protozoal myeloencephalitis in horses. Protective immune responses in horses have not been determined, but interferon-gamma (IFN-gamma) is considered critical for protection from neurologic disease in mice. The role of adaptive and innate immune responses in control of parasites was explored by infecting BALB/c, IFN-gamma knockout (GKO), and severe combined immune deficient (SCID) mice with S. neurona (10(4) sporocysts/mouse). Immune competent BALB/c mice eliminated parasites within 30 days, with no sign of neurologic disease, whereas GKO mice developed fulminant neurologic disease. In contrast, SCID mice remained healthy throughout the experimental period despite the persistence of parasite at low levels in some mice. Treatment with anti-IFN-gamma antibody resulted in neurologic disease in infected SCID mice. Although SCID mice lack adaptive immune responses, they have natural killer (NK) cells capable of producing significant quantities of IFN-gamma. Therefore, SCID mice were infected with sporocysts of S. neurona and treated with anti-asialo GM1. Depletion of NK cells, confirmed by flow cytometry, did not result in neurologic disease in SCID mice. These results indicate that IFN-gamma mediates protection from neurologic disease in SCID mice. Protective levels of IFN-gamma may originate from a low number of nondepleted NK cells or from a non-T cell, non-NK cell population.