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Isolation and Characterization of Extracellular Vesicles from Adult Schistosoma japonicum
Published on: May 22, 2018
Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity
Amy H Buck1, Gillian Coakley1, Fabio Simbari1
11] 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.
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.
Insights
Parasitic worms secrete RNA-filled vesicles called exosomes to manipulate host immunity. These exosomes suppress immune responses, revealing a conserved mechanism of inter-species RNA transfer in helminth infections.
Area of Science:
- Parasitology
- Molecular Biology
- Immunology
Background:
- RNA can be transferred between mammalian cells via vesicles.
- Helminths are parasitic worms that infect various hosts.
Purpose of the Study:
- To investigate if parasitic nematodes secrete RNA-containing vesicles.
- To determine the mechanism of helminth-host interaction involving RNA transfer.
Main Methods:
- Characterization of vesicles secreted by Heligmosomoides polygyrus.
- In vivo administration of nematode exosomes to mice.
- In vitro analysis of mouse cells incubated with nematode exosomes.
- Reporter assays to confirm miRNA-mediated gene repression.
Main Results:
- Heligmosomoides polygyrus secretes intestinal exosomes containing microRNAs (miRNAs), Y RNAs, and a nematode Argonaute protein.
- Nematode exosomes suppressed Type 2 innate immune responses and eosinophilia in mice.
- Nematode miRNAs were identified in the serum of mice infected with Litomosoides sigmodontis, indicating conserved miRNA secretion.
Conclusions:
- Exosomes represent a mechanism for helminths to transfer RNA and manipulate host responses.
- This study provides a framework for understanding RNA transfer between animal species.
- Helminth-derived exosomes can suppress host immune responses, impacting host-parasite dynamics.
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