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Cultivation of Heligmosomoides Polygyrus: An Immunomodulatory Nematode Parasite and its Secreted Products
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The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function

Allison J Bancroft1,2,3,4, Colin W Levy5, Thomas A Jowitt6,7

  • 1Lydia Becker Institute for Immunology and Inflammation, Manchester, M13 9PT, UK. allison.j.bancroft@manchester.ac.uk.

Nature Communications
|May 30, 2019
PubMed

Insights

Soil-transmitted helminth infections persist due to the non-immunogenic protein p43, which inhibits the key expulsion cytokine, interleukin-13 (IL-13). Understanding p43’s biology may lead to new treatments for Trichuris infections.

Area of Science:

  • Parasitology
  • Immunology
  • Molecular Biology

Background:

  • Soil-transmitted helminths like Trichuris spp. cause widespread infections in humans and animals.
  • Mechanisms driving chronic helminth infections remain poorly understood.

Purpose of the Study:

  • To investigate the role of the excretory/secretory protein p43 from Trichuris muris in chronic infection persistence.
  • To elucidate the molecular interactions of p43 with host immune factors.

Main Methods:

  • Protein characterization of T. muris excretory/secretory products.
  • Analysis of p43 sequence and structure, including homology searches.
  • In vitro and in vivo assays to assess p43 binding to interleukin-13 (IL-13) and its functional impact.
  • Investigation of p43 interaction with matrix proteoglycans.

Main Results:

  • p43 was identified as the most abundant protein in T. muris excretions/secretions and is non-immunogenic.
  • p43 exhibits homology to thrombospondin type 1 and IL-13 receptor α2.
  • p43 binds to IL-13, inhibiting its function in vitro and in vivo.
  • Tethering of p43 to matrix proteoglycans creates a reservoir for IL-13 interaction, potentially promoting chronic infection.

Conclusions:

  • p43 plays a critical role in enabling chronic Trichuris infections by neutralizing the host's immune response via IL-13 inhibition.
  • Targeting p43-IL-13 interactions offers a potential therapeutic strategy for controlling Trichuris infections.

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