Depletion of natural killer cells does not result in neurologic disease due to Sarcocystis neurona in mice with severe combined immunodeficiency.
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.
Sellon
Debra C
DC
Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington 99164, USA. dsellon@vetmed.wsu.edu
Knowles
Donald P
DP
Greiner
Ellis C
EC
Long
Maureen T
MT
Hines
Melissa T
MT
Hochstatter
Tressa
T
Hasel
Kristin M
KM
Ueti
Massaro
M
Gillis
Karen
K
Dame
John B
JB
D000818:Animals; D005260:Female; D006734:Horse Diseases / Q000276:immunology / Q000469:parasitology; D006736:Horses; D007121:Immunocompetence / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016513:Mice, SCID; D009422:Nervous System Diseases / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D016133:Polymerase Chain Reaction; D012522:Sarcocystis / Q000276:immunology / Q000472:pathogenicity; D012523:Sarcocystosis / Q000150:complications / Q000276:immunology / Q000662:veterinary*; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000276:immunology / Q000662:veterinary*; D013047:Specific Pathogen-Free Organisms
D007371:Interferon-gamma