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Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity
Open accessAbstract
Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα) and inhibits expression of the IL-33 receptor subunit ST2. Co-incubation with EV antibodies abrogated suppression of alternative activation and was associated with increased co-localization of the EVs with lysosomes. Furthermore, mice vaccinated with EV-alum generated protective immunity against larval challenge, highlighting an important role in vivo. In contrast, ST2-deficient mice are highly susceptible to infection, and they are unable to clear parasites following EV vaccination. Hence, macrophage activation and the IL-33 pathway are targeted by H. polygyrus EVs, while neutralization of EV function facilitates parasite expulsion.
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“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 Coakley et al., 2017
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“In H. polygyrus infections, these EVs target epithelial cells and macrophages, resulting in their loss of expression of the IL-33 receptor (IL-33R, also termed ST2) and downregulation of other immune genes.”
From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Coakley et al., 2017
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“Hence EVs are an adaptable part of the armory of helminth immunomodulators, allowing extracellular pathogens to manipulate events within host cells in a receptor-independent manner (Coakley et al., 2017).”
From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Coakley et al., 2017
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“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 Coakley et al., 2017
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“These effects result in suppression of both alternative and inflammatory macrophage activation (Coakley et al., 2017).”
From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Coakley et al., 2017
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Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules
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Metadata
- Authors
- Coakley, G., McCaskill, J. L., Borger, J. G., Simbari, F., Robertson, E., Millar, M., Harcus, Y., McSorley, H. J., Maizels, R. M., & Buck, A. H.
- Affiliations
- Centre for Immunity, Infection and Evolution (GB)
- Centre for Inflammation Research (GB)
- Wellcome Centre for Molecular Parasitology (GB)
- Corresponding author
- Maizels, Rick M.
- Buck, Amy H.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 19
- Issue
- 8
- Pages
- 1545-1557
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5457486
- OpenAlex
- W2618954565
- Cited by
- 219
- References
- 53
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 32 · 2023: 23 · 2022: 21 · 2021: 22 · 2020: 38 · 2019: 23 · 2018: 21 · 2017: 4
- FWCI
- 20.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/J01446X/1)
- Wellcome Trust (AHB-097394, RMM-106122, 095831, 104111)
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
- Life Sciences › Immunology and Microbiology › Parasitology › Helminth infection and control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- extracellular vesicles, Heligmosomoides polygyrus, macrophage activation, alternative macrophage activation, vaccines, nematode infection, interleukin-6, TNF-α, Ym1, RELMα, protective immunity
- MeSH terms
- Extracellular Vesicles, Interleukin-1 Receptor-Like 1 Protein, Animals, Antibodies, Helminth, Antibody Formation, Bone Marrow Cells, Immunity, Macrophage Activation, Macrophages, Nematospiroides dubius, Parasites, Vaccination, Vaccines, Cytochalasin D, Receptors, Interleukin, Mice
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