Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/112397
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice
Author: Eichenberger, R.
Ryan, S.
Jones, L.
Buitrago, G.
Polster, R.
de Oca, M.
Zuvelek, J.
Giacomin, P.
Dent, L.
Engwerda, C.
Field, M.
Sotillo, J.
Loukas, A.
Citation: Frontiers in Immunology, 2018; 9(APR):850-1-850-14
Publisher: Frontiers Media
Issue Date: 2018
ISSN: 1664-3224
1664-3224
Statement of
Responsibility: 
Ramon M. Eichenberger, Stephanie Ryan, Linda Jones, Geraldine Buitrago, Ramona Polster, Marcela Montes de Oca, Jennifer Zuvelek, Paul R. Giacomin, Lindsay A. Dent, Christian R. Engwerda, Matthew A. Field, Javier Sotillo and Alex Loukas
Abstract: Gastrointestinal (GI) parasites, hookworms in particular, have evolved to cause minimal harm to their hosts, allowing them to establish chronic infections. This is mediated by creating an immunoregulatory environment. Indeed, hookworms are such potent suppressors of inflammation that they have been used in clinical trials to treat inflammatory bowel diseases (IBD) and celiac disease. Since the recent description of helminths (worms) secreting extracellular vesicles (EVs), exosome-like EVs from different helminths have been characterized and their salient roles in parasite-host interactions have been highlighted. Here, we analyze EVs from the rodent parasite Nippostrongylus brasiliensis, which has been used as a model for human hookworm infection. N. brasiliensis EVs (Nb-EVs) are actively internalized by mouse gut organoids, indicating a role in driving parasitism. We used proteomics and RNA-Seq to profile the molecular composition of Nb-EVs. We identified 81 proteins, including proteins frequently present in exosomes (like tetraspanin, enolase, 14-3-3 protein, and heat shock proteins), and 27 sperm-coating protein-like extracellular proteins. RNA-Seq analysis revealed 52 miRNA species, many of which putatively map to mouse genes involved in regulation of inflammation. To determine whether GI nematode EVs had immunomodulatory properties, we assessed their potential to suppress GI inflammation in a mouse model of inducible chemical colitis. EVs from N. brasiliensis but not those from the whipworm Trichuris muris or control vesicles from grapes protected against colitic inflammation in the gut of mice that received a single intraperitoneal injection of EVs. Key cytokines associated with colitic pathology (IL-6, IL-1β, IFNγ, and IL-17a) were significantly suppressed in colon tissues from EV-treated mice. By contrast, high levels of the anti-inflammatory cytokine IL-10 were detected in Nb-EV-treated mice. Proteins and miRNAs contained within helminth EVs hold great potential application in development of drugs to treat helminth infections as well as chronic non-infectious diseases resulting from a dysregulated immune system, such as IBD.
Keywords: nematode; colitis; immunomodulation; parasite–host interaction; miRNA; proteomics; exosome; extracellular vesicles
Description: Published: 30 April 2018
Rights: Copyright © 2018 Eichenberger, Ryan, Jones, Buitrago, Polster, Montes de Oca, Zuvelek, Giacomin, Dent, Engwerda, Field, Sotillo and Loukas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
RMID: 0030088757
DOI: 10.3389/fimmu.2018.00850
Grant ID: http://purl.org/au-research/grants/nhmrc/1037304
Appears in Collections:Molecular and Biomedical Science publications

Files in This Item:
File Description SizeFormat 
hdl_112397.pdfPublished version7.04 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.