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The immune-modulatory potential of helminth-derived proteins in cellular models of inflammation: a systematic review with cross-study quantitative data analysis
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  • Published: 04 March 2026

The immune-modulatory potential of helminth-derived proteins in cellular models of inflammation: a systematic review with cross-study quantitative data analysis

  • Sienna Stucke1,
  • Aonghus Feeney1,
  • Richard Lalor2,
  • Sheila Donnelly2,
  • John Pius Dalton2,
  • Declan McKernan1 &
  • …
  • Eilís Dowd1 

Scientific Reports , Article number:  (2026) Cite this article

  • 1063 Accesses

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Immunology
  • Microbiology

Abstract

Helminths are parasitic worms that secrete a plethora of immune regulatory molecules which allow them to moderate inflammatory responses by their host’s immune system to ensure their survival within the host. This ability to drive a compatible existence with their host has led to research into the potential therapeutic effects of helminth-derived molecules the regulation of overactive immune and inflammatory responses in a wide variety of diseases. This systematic review with cross-study quantitative data analysis aims to synthesize the published data on helminth-derived immunomodulatory peptides/polypeptides/proteins (HDIPs) with a focus on determining the extent to which they modulate the inflammatory response in in vitro cellular models of inflammation. In accordance with PRISMA 2020 guidelines, a predefined systematic search of the PubMed, Web of Science and Medline databases identified relevant studies published up to September 2025, and 79 articles were included after screening. We found that most published studies used LPS or Concanavalin A stimulated macrophages, peripheral blood mononuclear cells or dendritic cells as the cellular model of inflammation. Twenty helminth species from which > 60 isolated HDIPs were derived were tested in these models, with the nematodes, Haemonchus contortus and Acanthocheilonema viteae, and the trematode, Fasciola hepatica, the most explored species. A common property of these molecules was the ability to significantly reduce the expression or production of pro-inflammatory cytokines such as IL-12, IL-1β, IL-6 and TNF, and significantly increase the expression or production of anti-inflammatory cytokines such as IL-10, TGFβ and IL-4. The effects on other cytokines, including IFNγ which is known to have both pro- and anti-inflammatory effects, were less consistent, with HDIPs either decreasing or increasing the levels of this cytokine. This systematic review with cross-study quantitative data analysis synthesizes the existing literature in this field and shows that the HDIPs secreted by several helminth species have consistently demonstrated effects though modification of cytokine levels and, as such, have therapeutic potential in conditions in which overactive immune and inflammatory responses play a pathogenic role.

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Data availability

All data is available in the Supplementary Excel file.

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Acknowledgements

SS is funded by the Parkinson’s Disease Research Award from Tony & Peigí O’Donoghue through the Galway University Foundation. ED would also like to acknowledge grants from the Michael J Fox Foundation for Parkinson’s Research (Grant Numbers: 17244 and 023410).

Funding

SS is funded by the Parkinson’s Disease Research Award from Tony & Peigí O’Donoghue through the Galway University Foundation. ED would also like to acknowledge grants from the Michael J Fox Foundation for Parkinson’s Research (Grant Numbers: 17244 and 023410).

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Authors and Affiliations

  1. Pharmacology & Therapeutics, Galway Neuroscience Centre, Institute for Health Discovery and Innovation, School of Pharmacy and Medical Sciences, University of Galway, Galway, Ireland

    Sienna Stucke, Aonghus Feeney, Declan McKernan & Eilís Dowd

  2. Molecular Parasitology Laboratory, Centre for One Health, Ryan Institute, School of Natural Sciences, University of Galway, Galway, Ireland

    Richard Lalor, Sheila Donnelly & John Pius Dalton

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  1. Sienna Stucke
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SS, AF and ED led the design and implementation of the systematic review, and wrote the first draft of the manuscript; RL, SD, JPD and DMK provided expert input into the drafts of the manuscript.

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Correspondence to Eilís Dowd.

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Stucke, S., Feeney, A., Lalor, R. et al. The immune-modulatory potential of helminth-derived proteins in cellular models of inflammation: a systematic review with cross-study quantitative data analysis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38162-x

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  • Received: 15 September 2025

  • Accepted: 29 January 2026

  • Published: 04 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-38162-x

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Keywords

  • Parasitic worms
  • Helminth
  • Helminth-derived peptides
  • Inflammation
  • Cytokines
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