Investigation of the Immunopathogenesis of Equine Protozoal Myeloencephalitis (EPM)

Investigation of the Immunopathogenesis of Equine Protozoal Myeloencephalitis (EPM) Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses in the Americas, and it is caused by the parasite Sarcocystis neurona. Although seroprevalence to S. neurona is usually high, EPM incidence is reported to be less than 1%. EPM development have been associated with breed, age, and stress, but specific factors such as immunogenetic predisposition and host-parasite interactions remains undetermined. Hence, our overall goal is to define the hallmarks for neuroinflammation in horses with EPM comparing with horses affected by other neurologic diseases and healthy controls. Our hypothesis is that an impaired pro-resolving immune response is a key component of EPM immunopathogenesis, and our objective is to elucidate if S. neurona infection exhausts the immune-mediated homeostatic response, driving overt inflammation and contributing to disease progression. To accomplish that, cellular immunity and soluble mediators in EPM horses will be investigated. In Aim 1, the cellular, cytokine and chemokine profile of immune cells at the site of S. neurona lesion in the central nervous system (CNS) of horses will be defined. Our approach to Aim 1 is to use immunohistochemistry to identify cell populations in EPM cases. In Aim 2, the main soluble mediators associated with EPM in serum and cerebrospinal fluid (CSF) of affected horses will be interrogated. Our approach to Aim 2 is to use a combination of Enzyme-linked Immunosorbent Assays (ELISAs) to assess the association between antibody titers against S. neurona with cytokine levels in EPM horses. Additionally, a targeted lipidomic analysis will be performed to define the levels of eicosanoids and SPM in serum and CSF of normal and neurologically impaired horses. Collectively, this set of experiments will allow us to better understand the immunopathology of EPM. Moreover, this research has the potential to identify biomarkers of S. neurona infection, providing the groundwork for novel ancillary diagnosis and immunomodulatory therapies for EPM. 1