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.
authors.affiliation: 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.
authors.forename: Amy H
authors.initials: AH
authors.lastname: Buck
authors.affiliation: 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.
authors.forename: Gillian
authors.initials: G
authors.lastname: Coakley
authors.affiliation: 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.
authors.forename: Fabio
authors.initials: F
authors.lastname: Simbari
authors.affiliation: 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.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: McSorley
authors.affiliation: 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.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Quintana
authors.affiliation: 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.
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Bihan
authors.affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
authors.forename: Sujai
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Laboratorio Nacional de Genómica para la Biodiversidad, Langebio-CINVESTAV, Irapuato 36821, Guanajuato, México.
authors.forename: Cei
authors.initials: C
authors.lastname: Abreu-Goodger
authors.affiliation: 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.
authors.forename: Marissa
authors.initials: M
authors.lastname: Lear
authors.affiliation: 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.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Harcus
authors.affiliation: Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ceroni
authors.affiliation: Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Babayan
authors.affiliation: 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.
authors.forename: Mark
authors.initials: M
authors.lastname: Blaxter
authors.affiliation: Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
authors.forename: Alasdair
authors.initials: A
authors.lastname: Ivens
authors.affiliation: 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.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
mesh_terms: D000528:Alternaria / Q000276:immunology / Q000502:physiology; D060487:Alternariosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D000818:Animals; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000276:immunology; D055354:Exosomes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D000072179:Interleukin-1 Receptor-Like 1 Protein; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009348:Nematoda / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009349:Nematode Infections / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D018510:RNA, Helminth / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology
chemical_list: C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D035683:MicroRNAs; D018510:RNA, Helminth; D018123:Receptors, Interleukin; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse