Helminth infection induces neuroimmune remodeling and clinical remission in a mouse model of multiple sclerosis 2260051

Abstract Introduction The central nervous system (CNS) is under constant immunosurveillance and is influenced by immune-related effector molecules, including type 2-associated cytokines, which have been shown to support healthy CNS function in a variety of contexts. Long-lasting type 2 immunity elicited by intestinal helminth infections can modify immune responses and wound repair locally and in peripheral tissues, but direct effects of helminth infection on the CNS are poorly understood. Here, we explore whether naturally evoked type 2 immune responses can modify neuroimmune interactions for therapeutic gain in a mouse model of multiple sclerosis. Methods Trichinella spiralis (Ts) is a helminth that infects both mice and humans, enabling identification of translationally relevant pathways of helminth-induced immunomodulation. Following Ts infection, mice were induced with experimental autoimmune encephalomyelitis (EAE) as a model of autoimmune neuroinflammation, and evaluated clinically, histologically, and immunologically with a particular focus on immune modulation within the CNS. Results Chronic infection with Ts remodelled the neuroimmune landscape, including establishment of a robust population of CNS-resident T helper (Th)2 cells and transient activation of microglia. Upon EAE induction, demyelination and infiltration of inflammatory Th17s into the CNS were reduced and resulted in clinical remission of EAE symptoms. Clinical remission was Stat6-dependent, relied on formation of CNS-resident immune populations, and could be promoted by adoptive transfer of Th2 cells in the absence of overt infection, highlighting the potential for helminth-primed Th2s to prevent neuroinflammation. Clinical remission and reduction of CNS-infiltrating Th17s could be induced therapeutically in relapsing-remitting EAE, suggesting therapeutic potential for helminth-mediated immunomodulation. Conclusion These findings highlight the potential for harnessing type 2 immunity to modify outcomes of neuroinflammation and neurodegeneration. Funding Source MS Canada, Canadian Institutes for Health Research, Research Corporation for Science Advancement, National Institutes of Health, Praespero Autoimmune Research Fund, Rutgers Busch Biomedical Grant Program Topic Categories Neuroimmunology (NEUR)