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

Buck, A. H. et al. (2014) Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nature Communications, 5(5488), (doi:10.1038/ncomms6488)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Babayan, Dr Simon
Authors: 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., and Maizels, R. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2014 Macmillan Publishers Limited
First Published:First published in Nature Communications 5:5488
Publisher Policy:Reproduced under a Creative Commons License

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