Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity
By A. Buck, G. Coakley, Fabio Simbari, H. McSorley, Juan F. Quintana, T. Le Bihan, Sujai Kumar, Cei Abreu-Goodger, M. Lear, Y. Harcus and 5 more. Nature Communications, 2014
733 citations recorded by the source corpus.
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. Mammalian cell-derived exosomes can carry RNA and proteins from cell to cell, but this mode of transport has not been shown in nematodes. Here the authors show that a gastrointestinal parasite secretes exosomes that transfer microRNAs to mammalian cells and regulate innate immunity.
Subfields: Ecology, Molecular Biology, Parasitology
View Paper: https://www.semanticscholar.org/paper/c9dd80f9ae29836dde12a215145ea255b9eea5f8
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Citations in the corpus
- Biological properties of extracellular vesicles and their physiological functions (2015, background): “via EVs, where they regulated host genes associated with immunity and inflammation and suppressed the innate type 2 response in vivo (616,617) suggesting that this may be a common feature for parasitic helminths (618).”
- Obstacles and opportunities in the functional analysis of extracellular vesicle RNA – an ISEV position paper (2017, background): “encapsulation in the vesicle membrane; for example, in nematode-derived EVs, full length YRNAs were found exclusively inside EVs whereas fragments were found outside EVs.[75]”
- Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper (2015, background): “polygyrus suppresses type 2 innate responses and eosinophilia in a rodent model of allergy (195).”
- miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis (2016, background): “More recently, it has been shown that miRNAs may play important roles in host–parasite interactions (3), host-gut microbiota interactions (4) as well as in transgenerational epigenetic inheritance (5).”