Depletion of natural killer cells does not result in neurologic disease due to Sarcocystis neurona in mice with severe combined immunodeficiency.

The study investigates the role of natural killer cells in preventing neurologic disease caused by Sarcocystis neurona, a parasite causing illness in horses, in mice with severe combined immunodeficiency (SCID). The results suggest that interferon-gamma mediates protection from this disease and that its protective levels could be produced by undiminished natural killer cells or another non-T cell, non-NK cell population.

Objective and Methodology

• The objective of the study was to understand the role of adaptive and innate immune responses in controlling the parasites caused by Sarcocystis neurona.
• Three types of mice were used for the study – BALB/c, IFN-gamma knockout (GKO) and severe combined immune deficient (SCID) mice.
• All mice were infected with S. neurona sporocysts and their responses were tracked.

Findings

• The immune competent BALB/c mice eliminated the parasites within 30 days with no signs of neurologic disease. On the other hand, the IFN-gamma knockout mice developed severe neurologic disease.
• Interestingly, the SCID mice seemed to remain healthy throughout the study period despite having some traces of the parasite. Further analysis showed that treating infected SCID mice with an anti-IFN-gamma antibody resulted in neurologic disease.
• Given that SCID mice lack adaptive immune responses but have natural killer (NK) cells with the ability to produce abundant amounts of IFN-gamma, they may play a role in preventing neurologic disease. To test this, some SCID mice infected with S. neurona were treated with anti-asialo GM1 (a substance used to deplete NK cells).
• However, even after depletion of the NK cells (as confirmed by flow cytometry), the SCID mice did not develop neurologic disease. This suggested that while IFN-gamma does provide protection against neurologic disease, this protection isn’t strictly dependent on NK cells.

Conclusion

• The study concluded that IFN-gamma mediates protection from neurologic disease in SCID mice against the S. neurona parasite.
• The protective levels of IFN-gamma may originate from either a low number of remaining NK cells or from a population that does not consist of T cells or NK cells. Further research would be required to validate these findings.