Helminth Imprinting of Hematopoietic Stem Cells Sustains Anti-Inflammatory Trained Innate Immunity That Attenuates Autoimmune Disease

Abstract Certain proinflammatory stimuli can metabolically and epigenetically modify monocytes/macrophages or NK cells to be more responsive secondary stimuli, a process known as trained innate immunity. However, the longevity of immunity is unclear. In this study, we report that Fasciola hepatica excretory-secretory products (FHES) imprint an anti-inflammatory phenotype on long-term hematopoietic stem (HSCs) monocyte precursor populations, enhancing their proliferation differentiation into Ly6Clow monocytes. These monocytes expand populate multiple compartments within mice, conferring hyporesponsiveness reduced susceptibility induction experimental autoimmune encephalomyelitis. Mice treated with FHES had enhanced alternatively activated macrophages, Th1 Th17 responses, attenuating effects autoimmunity persisted for 8 mo. Furthermore, transplantation HSCs from FHES-treated mice transferred naive mice. Our findings demonstrate helminth modulate promote development myeloid attenuate T cell–mediated disease.