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Nat Commun. 2014 Nov 25;5:5488. doi: 10.1038/ncomms6488.

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

Author information

1
1] Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK [2] Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
2
1] Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK [2] SynthSys, Centre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
3
Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
4
Laboratorio Nacional de Genómica para la Biodiversidad, Langebio-CINVESTAV, Irapuato 36821, Guanajuato, México.
5
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
6
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
7
1] Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK [2] SynthSys, Centre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK [3] Edinburgh Genomics, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.

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.

PMID:
25421927
PMCID:
PMC4263141
DOI:
10.1038/ncomms6488
[Indexed for MEDLINE]
Free PMC Article

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