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

Amy H. Buck; Gillian Coakley; Fabio Simbari; Henry J. McSorley; Juan F. Quintana; Thierry Le Bihan; Sujai Kumar; Cei Abreu-Goodger; Marissa Lear; Yvonne Harcus; Alessandro Ceroni; Simon A. Babayan; Mark Blaxter; Alasdair Ivens; Rick M. Maizels

doi:10.1038/ncomms6488

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

Amy H. Buck (Lead / Corresponding author), Gillian Coakley, Fabio Simbari, Henry J. McSorley, Juan F. Quintana, Thierry Le Bihan, Sujai Kumar, Cei Abreu-Goodger, Marissa Lear, Yvonne Harcus, Alessandro Ceroni, Simon A. Babayan, Mark Blaxter, Alasdair Ivens, Rick M. Maizels

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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.

Original language	English
Article number	5488
Pages (from-to)	1-11
Number of pages	11
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6488
Publication status	Published - 25 Nov 2014

Keywords

Innate immunity
miRNAs
Parasitic infection

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms6488Licence: CC BY

Final Published VersionFinal published version, 2.45 MBLicence: CC BY

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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. (2014). Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nature Communications, 5, 1-11. Article 5488. https://doi.org/10.1038/ncomms6488

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title = "Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity",

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.",

keywords = "Innate immunity, miRNAs, Parasitic infection",

author = "Buck, {Amy H.} and Gillian Coakley and Fabio Simbari and McSorley, {Henry J.} and Quintana, {Juan F.} and {Le Bihan}, Thierry and Sujai Kumar and Cei Abreu-Goodger and Marissa Lear and Yvonne Harcus and Alessandro Ceroni and Babayan, {Simon A.} and Mark Blaxter and Alasdair Ivens and Maizels, {Rick M.}",

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doi = "10.1038/ncomms6488",

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Buck, AH, Coakley, G, Simbari, F, McSorley, HJ, Quintana, JF, Le Bihan, T, Kumar, S, Abreu-Goodger, C, Lear, M, Harcus, Y, Ceroni, A, Babayan, SA, Blaxter, M, Ivens, A & Maizels, RM 2014, 'Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity', Nature Communications, vol. 5, 5488, pp. 1-11. https://doi.org/10.1038/ncomms6488

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AU - Buck, Amy H.

AU - Coakley, Gillian

AU - Simbari, Fabio

AU - McSorley, Henry J.

AU - Quintana, Juan F.

AU - Le Bihan, Thierry

AU - Kumar, Sujai

AU - Abreu-Goodger, Cei

AU - Lear, Marissa

AU - Harcus, Yvonne

AU - Ceroni, Alessandro

AU - Babayan, Simon A.

AU - Blaxter, Mark

AU - Ivens, Alasdair

AU - Maizels, Rick M.

PY - 2014/11/25

Y1 - 2014/11/25

N2 - 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.

AB - 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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ER -

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

Abstract

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ASJC Scopus subject areas

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Erratum: Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity(Nature Communications (2014) 5(5488) 10.1038/ncomms6488)

McSorley, Henry

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

Abstract

Keywords

ASJC Scopus subject areas

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Erratum: Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity(Nature Communications (2014) 5(5488) 10.1038/ncomms6488)

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McSorley, Henry

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