Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication

Eichenberger, Ramon M., Hasanuzzaman, Talukder, Field, Matt A., Wangchuk, Phurpa, Giacomin, Paul, Loukas, Alex, and Sotillo, Javier (2018) Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication. Journal of Extracellular Vesicles, 7 (1). 1428004.

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Abstract

Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where they orchestrate a parasitic existence. Herein we provide the first comprehensive characterization of the excretory/secretory products of T. muris. We identify 148 proteins secreted by T. muris and show for the first time that the mouse whipworm secretes exosome-like extracellular vesicles (EVs) that can interact with host cells. We use an Optiprep® gradient to purify the EVs, highlighting the suitability of this method for purifying EVs secreted by a parasitic nematode. We also characterize the proteomic and genomic content of the EVs, identifying >350 proteins, 56 miRNAs (22 novel) and 475 full-length mRNA transcripts mapping to T. muris gene models. Many of the miRNAs putatively mapped to mouse genes are involved in regulation of inflammation, implying a role in parasite-driven immunomodulation. In addition, for the first time to our knowledge, colonic organoids have been used to demonstrate the internalization of parasite EVs by host cells. Understanding how parasites interact with their host is crucial to develop new control measures. This first characterization of the proteins and EVs secreted by T. muris provides important information on whipworm–host communication and forms the basis for future studies.

Item ID: 49523
Item Type: Article (Research - C1)
ISSN: 2001-3078
Keywords: extracellular vesicles; exosomes; Trichuris muris; whipworm; miRNA; proteomics; organoids
Additional Information:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted Non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Funders: National Health and Medical Research Council (NHMRC), Swiss National Science Foundation (SNSF), Endeavour Research Fellowship
Projects and Grants: NHMRC programme grant number 1037304, NHMRC Principal Research Fellowship, SNSF Early Postdoctoral Mobility Fellowship P2ZHP3_161693
Date Deposited: 21 Mar 2018 23:26
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 40%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 30%
97 EXPANDING KNOWLEDGE > 970107 Expanding Knowledge in the Agricultural and Veterinary Sciences @ 30%
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