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

Research output: Contribution to journalArticlepeer-review

373 Citations (Scopus)
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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 languageEnglish
Article number5488
Pages (from-to)1-11
Number of pages11
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 25 Nov 2014

Keywords

  • Innate immunity
  • miRNAs
  • Parasitic infection

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