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

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Article number5488
Number of pages12
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 25 Nov 2014

Cite this

Buck, Amy H. ; Coakley, Gillian ; Simbari, Fabio ; McSorley, Henry J. ; Quintana, Juan F. ; Le Bihan, Thierry ; Kumar, Sujai ; Abreu-Goodger, Cei ; Lear, Marissa ; Harcus, Yvonne ; Ceroni, Alessandro ; Babayan, Simon A. ; Blaxter, Mark ; Ivens, Alasdair ; Maizels, Rick M. / Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. In: Nature Communications. 2014 ; Vol. 5.
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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.",
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.}",
year = "2014",
month = "11",
day = "25",
doi = "10.1038/ncomms6488",
language = "English",
volume = "5",
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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. https://doi.org/10.1038/ncomms6488

Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. / Buck, Amy H.; Coakley, Gillian; Simbari, Fabio; McSorley, Henry J.; Quintana, Juan F.; Le Bihan, Thierry; Kumar, Sujai; Abreu-Goodger, Cei; Lear, Marissa; Harcus, Yvonne; Ceroni, Alessandro; Babayan, Simon A.; Blaxter, Mark; Ivens, Alasdair; Maizels, Rick M.

In: Nature Communications, Vol. 5, 5488, 25.11.2014.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Buck, Amy H.

AU - Coakley, Gillian

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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.

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