Immunomodulatory Activity and Therapeutic Potential of the Filarial Nematode Secreted Product, ES-62

ES-62 is a protein that is actively secreted by filarial nematodes during parasitism of the vertebrate host. The molecule is able to direcdy interact with a number of cells of the immune system including B-lymphocytes, dendritic cells, macrophages and mast cells. Interaction appears to be dependent on complexing with TLR4 and results in modulation of the activity of a number of signal transduction molecules including MAP kinases, PI-3 kinase and NF-κB. Immunomodulatory activity of ES-62 appears to be largely due to the presence of phosphorylcholine (PC) moieties covalendy attached to N-type glycans. The net effect of ES-62’s interaction with the immune system is the generation of an antiinflammatory immunological phenotype. As a consequence of this, ES-62 demonstrates striking drug-like activity in models of disease associated with aberrant inflammation, in particular those associated with autoimmunity and allergy.