Antigen receptor signaling is subverted by an immunomodulatory product secreted by a filarial nematode.
ES-62 is a phosphorylcholine (PC)-containing glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae which is able to inhibit antigen receptor-stimulated proliferation of B and T lymphocytes in vitro and in vivo. The active component of ES-62 appears to be PC, as the results obtained with ES-62 are broadly mimicked by PC conjugated to bovine serum albumin or PC alone. Such desensitization of lymphocyte responsiveness appears to reflect an uncoupling of the antigen receptors from key intracellular proliferative signaling events, such as the phosphoinositide-3-kinase, protein kinase C and Ras mitogen-activating protein kinase pathways. ES-62 mediates such immunomodulatory effects at concentrations equivalent to those found for PC-containing molecules in the bloodstream of parasitized humans and, thus, ES-62 provides a model system for dissecting the mechanisms of immune evasion induced by related PC-containing glycoproteins expressed by human filarial nematodes.
Harnett
M M
MM
Department of Immunology, University of Glasgow, UK. M.Harnett@bio.gla.ac.uk
Harnett
W
W
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D004153:Dipetalonema / Q000276:immunology; D005368:Filariasis / Q000276:immunology; D005370:Filarioidea / Q000276:immunology* / Q000472:pathogenicity; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015801:Helminth Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D018448:Models, Immunological; D011493:Protein Kinase C / Q000378:metabolism; D011946:Receptors, Antigen / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018631:ras Proteins / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000947:Antigens, Helminth; C435884:ES-62 protein, Acanthocheilonema viteae; D006023:Glycoproteins; D015801:Helminth Proteins; D011946:Receptors, Antigen; D011493:Protein Kinase C; D018631:ras Proteins