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

Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity.
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线虫寄生虫分泌的外泌体将小的RN​​A转移到哺乳动物细胞上并调节先天免疫。

DOI:
10.1038/ncomms6488
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发表时间:
2014-11-25
影响因子:
16.6
通讯作者:
Maizels, Rick M.
Maizels, Rick M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Buck, Amy H.;Coakley, Gillian;Simbari, Fabio;McSorley, Henry J.;Quintana, Juan F.;Le Bihan, Thierry;Kumar, Sujai;Abreu-Goodger, Cei;Lear, Marissa;Harcus, Yvonne;Ceroni, Alessandro;Babayan, Simon A.;Blaxter, Mark;Ivens, Alasdair;Maizels, Rick M.

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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.
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