Helminth-induced modulation of neuroinflammation in a mouse model of multiple sclerosis

Abstract

Abstract Environmental factors play an important role in multiple sclerosis (MS) disease progression, but the exact cause remains unknown. The hygiene hypothesis suggests that a lack of exposure to microbes may alter disease susceptibility. Helminths in particular may play a role in preventing autoimmune disease due to the type 2 immune response they typically induce. Trichinella spiralis (Ts) first forms a transient intestinal infection followed by chronic infection where it exerts type 2 and regulatory immune responses, respectively. To evaluate the role of helminth infection in development and progression of MS, C57BL/6J mice were first chronically infected with Ts, then immunized with MOG35–55 to induce experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Ts-infected EAE mice have an altered disease course compared to uninfected controls, demonstrating delayed onset, reduced incidence, and symptom remission. Despite an overall decrease in lymphocyte recruitment to the central nervous system (CNS) in Ts/EAE mice, elevated numbers of infiltrating Th2 cells are maintained through the EAE disease course. In contrast, regulatory T cell expansion is dependent on the presence or absence of EAE symptoms. Histological analysis of cellular infiltration and demyelination in the spinal cord indicate limited demyelination with reduced infiltration into the parenchyma of Ts/EAE mice compared to EAE controls. Further immunophenotyping in the CNS to evaluate the contributions of infiltrating macrophages will be performed, as well as analyses of the cytokine milieu in the CNS. These results suggest that chronic Ts infection limits neuroinflammation, as shown by reduced clinical, immunological, and pathologic signs of EAE.