Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5–1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both. 1. Introduction Equine Protozoal Myeloencephalitis (EPM) represents the most commonly diagnosed neurologic disease of horses within the United States [1–3]. Horses are aberrant hosts and are commonly infected by ingestion of the Sarcocystis neurona sporocyst, through contamination of feedstuffs. The majority of horses exposed to this parasite generate a protective immune response and do not develop clinical signs. However, for the small percentage of horses that develop EPM, the clinical signs are classically those associated with asymmetric neurologic deficits, including gait abnormalities, ataxia, weakness, and focal muscle atrophy [3–5]. Annual losses in the United States are estimated to be $55.4 to $110.8 million [2]. In order to develop more efficacious treatments, vaccines, and diagnostic assays, it is important to first determine if there is an immune signature that dictates whether a horse will develop a protective response or neurologic disease. While protection has been linked to CD4 and CD8 cell-mediated response and interferon-gamma (IFN) production [6–9], the specific pathway(s) of immune cell responses associated with development of disease in the equine are still poorly characterized. Interestingly, a number of studies have reported an immune profile of decreased CD4 expression, surface antigen 1- (SAG1-) induced cell proliferation, PMA/I stimulated cell proliferation, and IFN in EPM affected horses [10–13]. It has
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