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Genome-wide expression analysis of the effects of a parasitic nematode's secreted exosomes on mammalian cells.

ABSTRACT: We show that a gastrointestinal nematode that infects mice, Heligmosomoides polygyrus, secretes vesicles packaged with specific microRNAs (miRNAs) and Y RNAs as well as a nematode-specific Argonaute protein. The vesicles are of intestinal origin and are enriched for homologs of mammalian proteins found in exosomes, including heat shock proteins, tetraspanins and an ESCORT protein. The nematode-derived vesicles are internalized by mouse intestinal epithelial cells and mediate changes in expression of host genes involved in inflammation and immunity, including the receptor for the alarmin IL33 as well as a key regulator of MAPK signaling, DUSP1.

ORGANISM(S): Mus musculus

PROVIDER: GSE55941 | GEO | 2014/12/24

SECONDARY ACCESSION(S): PRJNA241398

REPOSITORIES: GEO

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Genome-wide expression analysis of the effects of a parasitic nematode's secreted exosomes on mammalian cells.

Project description:We show that a gastrointestinal nematode that infects mice, Heligmosomoides polygyrus, secretes vesicles packaged with specific microRNAs (miRNAs) and Y RNAs as well as a nematode-specific Argonaute protein. The vesicles are of intestinal origin and are enriched for homologs of mammalian proteins found in exosomes, including heat shock proteins, tetraspanins and an ESCORT protein. The nematode-derived vesicles are internalized by mouse intestinal epithelial cells and mediate changes in expression of host genes involved in inflammation and immunity, including the receptor for the alarmin IL33 as well as a key regulator of MAPK signaling, DUSP1. A total of 12 samples were analyzed, from 4 different conditions: medium, exosome-treated, LPS and LPS+exosomes, each with 3 biological replicates. One of the 'medium' replicates was discarded due to outlier behaviour.

2014-12-24 | E-GEOD-55941 | biostudies-arrayexpress

Parasitic helminths repress the canonical intestinal stem cell program

Project description:The intestinal helminth parasite Heligmosomoides polygyrus initiates infection in mice by penetrating the duodenal mucosa, where it develops while surrounded by a multicellular granulomatous infiltrate before emerging into the intestinal lumen. We examined early H. polygyrus infection to assess the epithelial response to disruption of the mucosal barrier. Unexpectedly, intestinal stem cell markers, including Lgr5 and Olfm4, were completely lost in crypts overlying larvae-associated granulomas. We sought to identify the mechanism by which the H. polygyrus granuloma represses the activity of intestinal stem cells.

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2014-11-26 | E-GEOD-60021 | biostudies-arrayexpress

Exosomes secreted by a nematode parasite transfer small RNAs to mammalian cells and regulate genes of the innate immune system [Heligmosomoides polygyrus]

Project description:In mammalian systems, extracellular small RNAs can operate in a paracrine manner to communicate information between cells, relying on transport within vesicles. “Foreign” small RNAs derived from bacteria, plants and parasites have also been detected in mammalian body fluids, sparking interest in whether these could mediate inter-species communication. However, there is no mechanistic framework for RNA-mediated interspecies communication and the active movement of RNA via vesicles has not been shown outside of mammals. Here we demonstrate that specific microRNAs and Y RNAs are packaged into vesicles secreted by a gastrointestinal nematode, Heligmosomoides polygyrus, which naturally infects mice. Total RNA was extracted from the secretion product of adult worms and compared to the profile of small RNAs in adult worms, eggs and infective larvae.

2014-11-25 | E-GEOD-55978 | biostudies-arrayexpress

Exosomes secreted by a nematode parasite transfer small RNAs to mammalian cells and regulate genes of the innate immune system [Heligmosomoides polygyrus]

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RNAseq of murine small intestinal organoid cultures treated with Type 1 (IFNg) or Type 2 (IL4+IL13) cytokines in the presence or absence of excretory/secretory (ES) products of the helminth parasite Heligmosomoides polygyrus

Project description:Heligmosomoides polygyrus is a natural intestinal parasite of mice which exerts wide ranging modulatory effects on the immune system. This experiment was designed to investigate its abillity to modify intestinal epithelial cells, which form part of its natural niche. We tested gene expression in vitro, in differentiating organoids of small intestinal origin, exposed to cytokines and the released products of the parasite, termed HpES.

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