Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice

Eichenberger, Ramon M., Ryan, Stephanie, Jones, Linda, Buitrago, Geraldine, Polster, Ramona, Montes de Oca, Marcela, Zuvelek, Jennifer, Giacomin, Paul R., Dent, Lindsay A., Engwerda, Christian R., Field, Matthew A., Sotillo, Javier, and Loukas, Alex (2018) Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Frontiers in Immunology, 9.

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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 sup-pressors 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-1 beta, IFN gamma, 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.

Item ID: 53713
Item Type: Article (Research - C1)
ISSN: 1664-3224
Keywords: nematode, colitis, immunomodulation, parasite-host interaction, miRNA, proteomics, exosome, extracellular vesicles
Copyright Information: 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.
Funders: National Health and Medical Research Council (NHMRC), Swiss National Science Foundation (SNSF)
Projects and Grants: NHMRC 1037304, NHMRC Senior Principal Research Fellowship, SNSF P2ZHP3_161693
Date Deposited: 23 May 2018 07:38
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060406 Genetic Immunology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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