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Immunomodulatory activity and therapeutic potential of the filarial nematode secreted product, ES-62

Harnett, W. and Harnett, M.M. (2009) Immunomodulatory activity and therapeutic potential of the filarial nematode secreted product, ES-62. In: Pathogen-Derived Immunomodulatory Molecules. Advances in Experimental Medicine and Biology, 666 . Landes Bioscience, pp. 88-94. ISBN 978-1-4419-1600-6

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ES-62 is a protein that is actively secreted by filarial nematodes during parasitism of the vertebrate host. The molecule is able to directly 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-kappaB. Immunomodulatory activity of ES-62 appears to be largely due to the presence of phosphorylcholine (PC) moieties covalently attached to N-type glycans. The net effect of ES-62's interaction with the immune system is the generation of an anti-inflammatory 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.