1. The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62 Modulates Complement Activation.

    Journal of Biological Chemistry 291(22):11939 (2016) PMID 27044740 PMCID PMC4882459

    Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed...
  2. Brugia malayi Antigen (BmA) Inhibits HIV-1 Trans-Infection but Neither BmA nor ES-62 Alter HIV-1 Infectivity of DC Induced CD4+ Th-Cells.

    PLoS ONE 11(1):e0146527 (2016) PMID 26808476 PMCID PMC4726616

    One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may...
  3. Protective effect of small molecule analogues of the Acanthocheilonema viteae secreted product ES-62 on oxazolone-induced ear inflammation.

    Experimental Parasitology 158:18 (2015) PMID 25836375 PMCID PMC4659540

    ES-62 is the major secreted protein of the rodent filarial nematode Acanthocheilonema viteae. The molecule contains covalently attached phosphorylcholine (PC) residues, which confer anti-inflammatory properties on ES-62, underpinning the idea that drugs based on this active moiety may have thera...
  4. The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62.

    Immunology Letters 168(1):31 (2015) PMID 26343793 PMCID PMC4643489

    ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, has been shown to modulate the immune system through subversion of signal transduction pathways operating in various immune system cells. With respect to human bone marrow-derived mast cells (BMMCs), ES-62 was prev...
  5. Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome.

    Journal of Autoimmunity 60:59 (2015) PMID 25975491 PMCID PMC4459730

    Rheumatoid arthritis (RA) remains a debilitating autoimmune condition as many patients are refractory to existing conventional and biologic therapies, and hence successful development of novel treatments remains a critical requirement. Towards this, we now describe a synthetic drug-like small mo...
  6. The parasitic worm product ES-62 targets myeloid differentiation factor 88-dependent effector mechanisms to suppress antinuclear antibody production and proteinuria in MRL/lpr mice.

    Arthritis & rheumatology (Hoboken, N.J.) 67(4):1023 (2015) PMID 25546822 PMCID PMC4409857

    The hygiene hypothesis suggests that parasitic helminths (worms) protect against the development of autoimmune disease via a serendipitous side effect of worm-derived immunomodulators that concomitantly promote parasite survival and limit host pathology. The aim of this study was to investigate ...
  7. The immunomodulatory parasitic worm product ES-62 reduces lupus-associated accelerated atherosclerosis in a mouse model.

    International Journal for Parasitology 45(4):203 (2015) PMID 25666929 PMCID PMC4355381

    ES-62 is an anti-inflammatory phosphorylcholine-containing glycoprotein secreted by the filarial nematode Acanthocheilonema viteae. Accelerated atherosclerosis frequently occurs in systemic lupus erythematosus, resulting in substantial cardiovascular morbidity and mortality. We examined the effe...
  8. Small molecule analogues of the immunomodulatory parasitic helminth product ES-62 have anti-allergy properties.

    International Journal for Parasitology 44(9):669 (2014) PMID 24929132 PMCID PMC4119935

    ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, exhibits anti-inflammatory properties by virtue of covalently attached phosphorylcholine moieties. Screening of a library of ES-62 phosphorylcholine-based small molecule analogues (SMAs) revealed that two compounds...
  9. Secretory products of helminth parasites as immunomodulators.

    Molecular and Biochemical Parasitology 195(2):130 (2014) PMID 24704440

    Parasitic helminths release molecules into their environment, which are generally referred to as excretory-secretory products or ES. ES derived from a wide range of nematodes, trematodes and cestodes have been studied during the past 30-40 years, their characterization evolving from simple bioch...
  10. ES-62 protects against collagen-induced arthritis by resetting interleukin-22 toward resolution of inflammation in the joints.

    Arthritis & rheumatology (Hoboken, N.J.) 66(6):1492 (2014) PMID 24497523 PMCID PMC4737104

    The parasitic worm-derived immunomodulator ES-62 protects against disease in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis (RA) by suppressing pathogenic interleukin-17 (IL-17) responses. The Th17-associated cytokine IL-22 also appears to have a pathogenic role in auto...
  11. Protection against collagen-induced arthritis in mice afforded by the parasitic worm product, ES-62, is associated with restoration of the levels of interleukin-10-producing B cells and reduced plasma cell infiltration of the joints.

    Immunology 141(3):457 (2014) PMID 24708419 PMCID PMC3930382

    We have previously reported that ES-62, a molecule secreted by the parasitic filarial nematode Acanthocheilonema viteae, protects mice from developing collagen-induced arthritis (CIA). Together with increasing evidence that worm infection may protect against autoimmune conditions, this raises th...
  12. ES-62, a therapeutic anti-inflammatory agent evolved by the filarial nematode Acanthocheilonema viteae.

    Molecular and Biochemical Parasitology 194(1-2):1 (2014) PMID 24671112

    Filarial nematodes cause long-term infections in hundreds of millions of people. A significant proportion of those affected develop a number of debilitating health problems but, remarkably, such infections are often unnoticed for many years. It is well known that parasitic worms modulate, yet do...
  13. Designing anti-inflammatory drugs from parasitic worms: a synthetic small molecule analogue of the Acanthocheilonema viteae product ES-62 prevents development of collagen-induced arthritis.

    Journal of medicinal and pharmaceutical chemistry 56(24):9982 (2013) PMID 24228757 PMCID PMC4125414

    In spite of increasing evidence that parasitic worms may protect humans from developing allergic and autoimmune diseases and the continuing identification of defined helminth-derived immunomodulatory molecules, to date no new anti-inflammatory drugs have been developed from these organisms. We h...
  14. Reply: To PMID 22729944.

    Arthritis & Rheumatism 65(5):1403 (2013) PMID 23401057

  15. The helminth product, ES-62, protects against airway inflammation by resetting the Th cell phenotype.

    International Journal for Parasitology 43(3-4):211 (2013) PMID 23291461 PMCID PMC3584281

    We previously demonstrated inhibition of ovalbumin-induced allergic airway hyper-responsiveness in the mouse using ES-62, a phosphorylcholine-containing glycoprotein secreted by the filarial nematode, Acanthocheilonema viteae. This inhibition correlated with ES-62-induced mast cell desensitisati...
  16. Mast Cell Subsets and Their Functional Modulation by the Acanthocheilonema viteae Product ES-62.

    Journal of Parasitology Research 2013:961268 (2013) PMID 23476740 PMCID PMC3582060

    ES-62, an immunomodulator secreted by filarial nematodes, exhibits therapeutic potential in mouse models of allergic inflammation, at least in part by inducing the desensitisation of Fc ε RI-mediated mast cell responses. However, in addition to their pathogenic roles in allergic and autoimmune d...
  17. Allergy and parasites.

    Journal of Parasitology Research 2013:502562 (2013) PMID 23476739 PMCID PMC3583124

  18. The parasitic helminth product ES-62 suppresses pathogenesis in collagen-induced arthritis by targeting the interleukin-17-producing cellular network at multiple sites.

    Arthritis & Rheumatism 64(10):3168 (2012) PMID 22729944

    Among many survival strategies, parasitic worms secrete molecules that modulate host immune responses. One such product, ES-62, is protective against collagen-induced arthritis (CIA), a model of rheumatoid arthritis (RA). Since interleukin-17 (IL-17) has been reported to play a pathogenic role i...
  19. Receptor usage by the Acanthocheilonema viteae-derived immunomodulator, ES-62.

    Experimental Parasitology 132(1):97 (2012) PMID 21925176

    ES-62 is an immunomodulatory phosphorylcholine (PC)-containing glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae. Previously, the use of knockout mice has revealed the effects of ES-62 on macrophages and dendritic cells to be dependent on TLR4. However, it is possibl...
  20. Immunomodulatory properties of ES-62, a phosphorylcholine-containing glycoprotein secreted by Acanthocheilonema viteae.

    Endocrine, Metabolic and Immune Disorders - Dru... 12(1):45 (2012) PMID 22214333

    Filarial nematodes are parasites that have the ability to persist in their hosts for extended periods of time due to the employment of various mechanisms to divert or down-regulate the host's immune responses. One of these mechanisms is the production of immunomodulatory excretory-secretory (ES)...