Interferon gamma protective against Sarcocystis neurona encephalitis in susceptible murine model

Abstract

Sarcocystis neurona is the predominant etiological agent of the infectious equine neurologic disease, equine protozoal myeloencephalitis (EPM), which is prevalent in the United States. A wealth of knowledge about S. neurona biology and its life cycle has accumulated over the last several decades. However, much remains unknown about the aberrant equine host's immune response to S. neurona and the relatively high prevalence of exposure to the protozoa but relatively infrequent occurrence of clinical neurologic disease. Mouse models simulating EPM are commonly used to study the disease due to numerous challenges associated with studying the disease in horses. The critical role of the cytokine, interferon gamma (IFNγ), in protection against S. neurona encephalitis has been well established as Ifnγ^-/- mice are highly susceptible to S. neurona encephalitis. However, there are discrepancies in the literature regarding S. neurona disease susceptibility in lymphocyte deficient mice, lacking T-lymphocytes and their associated Ifnγ production. In the current study, we investigated S. neurona encephalitis susceptibility in 2 genetically different strains of lymphocyte null mice, C57Bl/6 (B6).scid and Balb/c.scid. The B6.scid mouse was determined to be susceptible to S. neurona encephalitis as 100 % of infected mice developed neurologic disease within 60 days post infection (DPI). The Balb/c.scid mouse was nearly disease resistant as only 10 % of mice developed neurologic disease 60 DPI. Encephalitis was histologically demonstrable and S. neurona was identified in cerebellar samples collected from B6.scid but absent in Balb/c.scid mice. To further investigate the importance of T-lymphocyte derived Ifnγ, T- lymphocytes were adoptively transferred into B6.scid mice. The adoptive transfer of Ifnγ competent T- lymphocytes offered complete protection against S. neurona encephalitis but transfer of Ifnγ deficient T- lymphocytes did not with 100 % of these recipient mice succumbing to S. neruona encephalitis. Histological analysis of collected cerebellar samples confirmed the presences of S. neurona and encephalitis in recipient mice that developed neurologic disease. These studies show that the background strain is critical in studying SCID susceptibility to S. neurona disease and suggest a protective role of Ifnγ producing T- lymphocytes in S. neurona encephalitis susceptible mice.

Keywords: Equine protozoal myeloencephalitis; Horse; Interferon gamma; Opossum; Sarcocystis neurona.