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 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.
Harnett
William
W
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. w.harnett@strath.ac.uk
Harnett
Margaret M
MM
D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy*; D005370:Filarioidea / Q000378:metabolism; D015801:Helminth Proteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*
C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; D007155:Immunologic Factors