ArticleScientific reports2016
The helminth product, ES-62 modulates dendritic cell responses by inducing the selective autophagolysosomal degradation of TLR-transducers, as exemplified by PKCδ.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- The immune-modulatory potential of helminth-derived proteins in cellular models of inflammation: a systematic review with cross-study quantitative data analysis.Scientific reports · 2026Pooled it
- Curtailment of Toll-like receptor signalling and cytokine production in dendritic cells by secreted products of Heligmosomoides polygyrus.PLoS pathogens · 2026Article
- Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation.Journal of advanced research · 2026Article
- Nematodes immunomodulatory mechanisms and possible clinical application.Frontiers in immunology · 2026Review
- Hydatid fluid fromFrontiers in cellular and infection microbiology · 2024Article
- Harnessing Immune Evasion Strategy of Lymphatic Filariae: A Therapeutic Approach against Inflammatory and Infective Pathology.Vaccines · 2022Review
- Suppression of inflammatory arthritis by the parasitic worm product ES-62 is associated with epigenetic changes in synovial fibroblasts.PLoS pathogens · 2021Article
- Mining Helminths for Novel Therapeutics.Trends in molecular medicine · 2021Review
- The gut-joint axis in rheumatoid arthritis.Nature reviews. Rheumatology · 2021Review
- Review
- Anti-inflammatory Trained Immunity Mediated by Helminth Products Attenuates the Induction of T Cell-Mediated Autoimmune Disease.Frontiers in immunology · 2019Article
- Article
- Failure of the Anti-Inflammatory Parasitic Worm Product ES-62 to Provide Protection in Mouse Models of Type I Diabetes, Multiple Sclerosis, and Inflammatory Bowel Disease.Molecules (Basel, Switzerland) · 2018Article
- Small Molecule Analogues of the parasitic worm product ES-62 interact with the TIR domain of MyD88 to inhibit pro-inflammatory signalling.Scientific reports · 2018Article
- Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles.Frontiers in immunology · 2018Review
- Dendritic cells provide a therapeutic target for synthetic small molecule analogues of the parasitic worm product, ES-62.Scientific reports · 2017Article
- From Christian de Duve to Yoshinori Ohsumi: More to autophagy than just dining at home.Biomedical journal · 2017Review
- TLR Specific Immune Responses against Helminth Infections.Journal of parasitology research · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
We have previously shown that ES-62, a phosphorylcholine (PC)-containing glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae targets dendritic cell (DC) responses, specifically by suppressing TLR4 signalling to inhibit Th1/Th17-driven inflammation. We have now investigated the molecular mechanisms underpinning such immunomodulation and show here that ES-62-mediated downregulation of protein kinase C-δ (PKC-δ), a TLR4-associated signalling mediator required for full activation of LPS-driven pro-inflammatory responses, is associated with induction of a low level of autophagic flux, as evidenced by upregulation and trafficking of p62 and LC3 and their consequent autophagolysosomal degradation. By contrast, the classical TLR4 ligand LPS, strongly upregulates p62 and LC3 expression but under such canonical TLR4 signalling this upregulation appears to reflect a block in autophagic flux, with these elements predominantly degraded in a proteasomal manner. These data are consistent with autophagic flux acting to homeostatically suppress proinflammatory DC responses and indeed, blocking of PKC-δ degradation by the autophagolysosomal inhibitors, E64d plus pepstatin A, results in abrogation of the ES-62-mediated suppression of LPS-driven release of IL-6, IL-12p70 and TNF-α by DCs. Thus, by harnessing this homeostatic regulatory mechanism, ES-62 can protect against aberrant inflammation, either to promote parasite survival or serendipitously, exhibit therapeutic potential in inflammatory disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.