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

被引：617

作者：

Buck, Amy H. ^{[1
,2
]}

Coakley, Gillian ^{[1
,2
]}

Simbari, Fabio ^{[1
,2
]}

McSorley, Henry J. ^{[1
,2
]}

Quintana, Juan F. ^{[1
,2
]}

Le Bihan, Thierry ^{[2
,3
]}

Kumar, Sujai ^{[4
]}

Abreu-Goodger, Cei ^{[5
]}

Lear, Marissa ^{[1
,2
]}

Harcus, Yvonne ^{[1
,2
]}

Ceroni, Alessandro ^{[1
]}

Babayan, Simon A. ^{[2
]}

Blaxter, Mark ^{[2
,3
,6
]}

Ivens, Alasdair ^{[2
]}

Maizels, Rick M. ^{[1
,2
]}

机构：

[1] Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, Edinburgh EH9 3FL, Midlothian, Scotland

[2] Univ Edinburgh, Sch Biol Sci, Ctr Immun Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland

[3] Univ Edinburgh, Sch Biol Sci, Ctr Synthet & Syst Biol, SynthSys, Edinburgh EH9 3BF, Midlothian, Scotland

[4] Univ Edinburgh, Sch Biol Sci, Inst Evolutionary Biol, Edinburgh EH9 3FL, Midlothian, Scotland

[5] Langebio CINVESTAV, Lab Nacl Genom Biodiversidad, Guanajuato 36821, Mexico

[6] Univ Edinburgh, Sch Biol Sci, Edinburgh Genom, Edinburgh EH9 3FL, Midlothian, Scotland

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

英国惠康基金;

关键词：

REGULATORY T-CELLS; PROTEOMIC ANALYSIS; MICRORNAS; REVEALS; GENES; COMMUNICATION; BIOGENESIS; INFECTION; TH2;

D O I：

10.1038/ncomms6488

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：11

共 53 条

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Many Families of C. elegans MicroRNAs Are Not Essential for Development or Viability [J].