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

ABSTRACT: 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.

ORGANISM(S): Heligmosomoides polygyrus

PROVIDER: GSE55978 | GEO | 2014/11/25

SECONDARY ACCESSION(S): PRJNA241496

REPOSITORIES: GEO

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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 [Litomosoides sigmodontis]

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 serum of mice infected with Litomosoides sigmodontis at 60 days post infection

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Project description: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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Genome sequencing of Heligmosomoides polygyrus bakeri

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Gene expression analysis of ex-Foxp3 Th2 cells during Heligmosomoides polygyrus infection

Project description:Gene expression of Treg cells that have lost Foxp3 expression and acquired Il4 expression following adoptive transfer into T-cell deficient mice (HpTR-IL-4gfp+), cmpared to conventional Treg cells isolated from H. polygyrus-infected wild-type mice (HpTR) and Th2 cells generated from naïve T cells following adoptive transfer into H. polygyrus-infected T-cell deficient mice (nT-IL-4gfp+). Immunity to intestinal helminth infections requires the rapid activation of T helper 2 (Th2) cells. However, simultaneous expansion of regulatory CD4+Foxp3+ T (Treg) cells impedes protective responses, resulting in chronic infections. The ratio between regulatory and effector T cells can therefore determine the outcome of infection. The re-differentiation of Treg into T helper (Th) cells has been identified in hyper-inflammatory diseases. In this study, we asked whether ex-Treg Th2 cells develop and contribute to type 2 immunity. Using multi-gene reporter and fate-reporter systems we demonstrate that a significant proportion of Th2 cells derive from Foxp3+ cells following Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus. Through selective deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting Treg cells into Th2 cells could concomitantly enhance Th2 cells and limit Treg-mediated suppression.

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The production of Excretory-Secretory molecules from Heligmosomoides polygyrus bakeri fourth stage larvae varies between mixed and single sex cultures.

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