ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential

Harnett, William; McInnes, Iain B.; Harnett, Margaret M.

doi:10.1016/j.imlet.2004.04.008

Cited by 58 publications

(32 citation statements)

References 54 publications

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“…Such a mutually beneficial effect of inhibition of the PAF response resembles observations with PAF receptor-deficient mice showing enhanced worm survival and decreased inflammation upon infection with the nematode Strongyloides venezuelensis (24). Finally, it should be noted that in addition to the development of PAF-reactive antibodies, PC-containing structures such as GP300 may also exert direct immunomodulating effects, as observed for ES-62, a filarial glycoprotein containing PC substituted to N-glycans (11). ES-62 interacts with B and T cells, dendritic cells, and macrophages, skewing the response to a Th2/anti-inflammatory phenotype.…”

Section: Discussionmentioning

confidence: 54%

Antibodies Elicited by the Bovine Lungworm,Dictyocaulus viviparus, Cross-React with Platelet-Activating Factor

et al. 2007

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Parasite N-glycans may play an important role in helminth infections. As antibodies from Dictyocaulus viviparus-infected calves strongly react with N-glycans, we investigated the characteristics of the major immunodominant glycoprotein (GP300) of this parasite. Probing of worm extracts with various lectins demonstrated unique binding of GP300 to wheat germ agglutinin. Analysis of lectin-purified GP300 revealed that the glycan was substituted with phosphorylcholine and reacted with the phosphorylcholine-specific antibody TEPC-15. Competitive enzyme-linked immunosorbent assay with GP300-coated plates and GP300-specific immunoglobulin G (IgG) in conjunction with free phosphorylcholine or TEPC-15 demonstrated that antibodies from infected calves recognized phosphorylcholine on GP300. Additional assays showed that these antibodies cross-reacted with the phosphorylcholine moiety present on platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-snglycero-3-phosphocholine), a proinflammatory mediator of the host. Heavily infected calves contained high levels of serum GP300-specific IgG1 but low levels of IgA and IgG2 and showed a reduced influx of eosinophils in the lungs, all consistent with a neutralization of PAF activity. In conclusion, we demonstrated that D. viviparus infection elicits GP300-specific antibodies that cross-react with PAF and may neutralize PAF function, thus limiting the development of a protective response as well as parasite-induced host pathology.

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Section: Discussionmentioning

confidence: 54%

Antibodies Elicited by the Bovine Lungworm,Dictyocaulus viviparus, Cross-React with Platelet-Activating Factor

et al. 2007

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“…Alternatively, immunosuppressive products secreted by helminths have considerable potential as immunotherapeutics. For example, ES-62 derived from Acanthocheilonema viteae attenuated the symptoms of collagen-induced arthritis (10) and Schistosoma mansoni soluble egg Ag (SEA) protected against EAE, colitis, and diabetes (11)(12)(13). Much of the evidence to date suggests that helminths suppress autoimmunity through the induction of Tregs (1).…”

mentioning

confidence: 99%

Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia

Finlay

Stefańska

Walsh

et al. 2016

The Journal of Immunology

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Epidemiologic studies in humans have demonstrated that infection with helminth parasites is associated with a reduced risk of developing autoimmune diseases. Mechanistic studies in mice have linked the protective effect of helminths on autoimmunity to the suppressive activity of helminth-induced regulatory T cells (Tregs) or Th2 cells. In this study, we demonstrate that treatment of mice with Fasciola hepatica excretory-secretory products (FHES) attenuated the clinical signs of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Protection was associated with a significant reduction in the infiltration of pathogenic Th1 and Th17 cells into the brain. Although FHES enhanced anti-inflammatory cytokine and Th2 responses, protection against EAE was independent of IL-4, IL-10, and Tregs. However, administration of FHES induced production of the type 2 cytokines IL-33 and IL-5, which promoted accumulation of eosinophils. FHES-induced expansion of eosinophils and protection against EAE was lost in IL-33−/− mice and upon neutralization of IL-5. Furthermore, transfer of FHES-induced or IL-33–induced eosinophils conferred protection against EAE. In addition, treatment of mice with recombinant IL-33 attenuated autoimmunity, and this was dependent on IL-5. To our knowledge, this study is the first to report a role for helminth-induced IL-5 and IL-33 in protection against autoimmunity.

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“…Many examples illustrate this potential of parasites' molecules or extracts employed in experimental models. For example, the filarial nematode secreted product ES-62 has been shown to have both prophylactic and therapeutic efficacy in a murine model of arthritis (Harnett et al 2004). Recently, anti-inflammatory ES-62 activity was found in synovial tissues from patients with rheumatoid arthritis (Harnett et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Host immune response to Toxoplasma gondii and Ascaris lumbricoides in a highly endemic area: evidence of parasite co-immunomodulation properties influencing the outcome of both infections

Bahia-Oliveira

Silva

Peixoto-Rangel

et al. 2009

Mem. Inst. Oswaldo Cruz

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ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential

Cited by 58 publications

References 54 publications

Antibodies Elicited by the Bovine Lungworm,Dictyocaulus viviparus, Cross-React with Platelet-Activating Factor

Antibodies Elicited by the Bovine Lungworm,Dictyocaulus viviparus, Cross-React with Platelet-Activating Factor

Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia

Host immune response to Toxoplasma gondii and Ascaris lumbricoides in a highly endemic area: evidence of parasite co-immunomodulation properties influencing the outcome of both infections

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