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Cited by 770Parasites and Host InteractionsExtracellular vesicles in diseaseParasitic Diseases Research and Treatment

Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity

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Buck, Amy H., Coakley, Gillian, Simbari, Fabio, McSorley, Henry J., Quintana, Juan F., Le Bihan, Thierry, Kumar, Sujai, Abreu-Goodger, Cei +7 more·2014·Nature Communications
DOI 10.1038/ncomms6488PMC PMC4263141
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Abstract

In mammalian systems RNA can move between cells via vesicles. Here we demonstrate that the gastrointestinal nematode Heligmosomoides polygyrus , which infects mice, secretes vesicles containing microRNAs (miRNAs) and Y RNAs as well as a nematode Argonaute protein. These vesicles are of intestinal origin and are enriched for homologues of mammalian exosome proteins. Administration of the nematode exosomes to mice suppresses Type 2 innate responses and eosinophilia induced by the allergen Alternaria. Microarray analysis of mouse cells incubated with nematode exosomes in vitro identifies Il33r and Dusp1 as suppressed genes, and Dusp1 can be repressed by nematode miRNAs based on a reporter assay. We further identify miRNAs from the filarial nematode Litomosoides sigmodontis in the serum of infected mice, suggesting that miRNA secretion into host tissues is conserved among parasitic nematodes. These results reveal exosomes as another mechanism by which helminths manipulate their hosts and provide a mechanistic framework for RNA transfer between animal species.

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  • H. polygyrus releases small RNA-containing extracellular vesicles that suppress transcription of the IL-33 receptor.

    “through the release of small RNA-containing extracellular vesicles that suppress transcription of the IL-33 receptor”

    From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Buck et al., 2014

    The Results section, “Regulation of mouse genes by nematode exosomes” (page unavailable), reports that H. polygyrus exosomes significantly reduce expression of the IL-33 receptor gene, validated by RT–qPCR. It does not establish that transcription itself is suppressed: the Discussion presents inhibited Il33r transcription as a possible indirect mechanism. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Helminths release extracellular vesicles, often termed exosomes, which are able to fuse and enter host cells, carrying with them a cargo of miRNAs.

    “A paradigm-shifting discovery has been that helminths release extracellular vesicles (EVs), often termed exosomes, which are able to fuse and enter host cells, carrying with them a cargo of miRNAs (Buck et al., 2014, Coakley et al., 2017).”

    From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Buck et al., 2014

    The Abstract reports that H. polygyrus secretes miRNA-containing vesicles, and Results (“Internalization of nematode exosomes and RNAs by mouse cells”; page unavailable) shows that the vesicles and parasite miRNAs enter mouse cells. The paper does not establish that the vesicles fuse with host cells; it demonstrates uptake, not the mechanism of entry. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • H. polygyrus EVs suppress Alternaria allergen-induced allergic airway responses.

    “and H. polygyrus EVs suppress Alternaria allergen-induced allergic airway responses (Buck et al., 2014).”

    From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Buck et al., 2014

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Authors
Buck, A. H., Coakley, G., Simbari, F., McSorley, H. J., Quintana, J. F., Le Bihan, T., Kumar, S., Abreu-Goodger, C., Lear, M., Harcus, Y., Ceroni, A., Babayan, S. A., Blaxter, M., Ivens, A., & Maizels, R. M.
Affiliations
  • Centre for Immunity, Infection and Evolution (GB)
  • University of Edinburgh (GB)
Corresponding author
Buck, Amy H.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2014-11-25
Volume
5
Issue
1
Pages
5488-5488
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms6488
PMC
PMC4263141
OpenAlex
W2125198788
Cited by
770
References
8
Citations by year
2026: 52 · 2025: 57 · 2024: 59 · 2023: 64 · 2022: 64 · 2021: 83 · 2020: 85 · 2019: 81 · 2018: 61 · 2017: 63 · 2016: 55 · 2015: 42 · 2014: 3
FWCI
39.67
Type
journal article
Language
en
Update notices
erratum (2015-10-22)
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (095831)
  • Asthma and Lung UK
  • Institut National de la Santé et de la Recherche Médicale
  • Biotechnology and Biological Sciences Research Council (1276234)
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Keywords
exosomes, parasitic nematodes, Heligmosomoides polygyrus, Litomosoides sigmodontis, microRNA, Y RNA, eosinophilia, MKP-1, serum microRNA, gastrointestinal nematodes
MeSH terms
Interleukin-1 Receptor-Like 1 Protein, Alternaria, Animals, Humans, Immunity, Innate, Mice, Inbred BALB C, Nematoda, Nematode Infections, Receptors, Interleukin, RNA, Helminth, MicroRNAs, Mice, Dual Specificity Phosphatase 1, Exosomes, Alternariosis

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