Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite-host cross talk

Eline P Hansen; Bastian Fromm; Sidsel D Andersen; Antonio Marcilla; Kasper L Andersen; Anne Borup; Andrew R Williams; Aaron R Jex; Robin B Gasser; Neil D Young; Ross S Hall; Allan Stensballe; Vladimir Ovchinnikov; Yan Yan; Merete Fredholm; Stig M Thamsborg; Peter Nejsum

doi:10.1080/20013078.2019.1578116

Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite-host cross talk

J Extracell Vesicles. 2019 Feb 14;8(1):1578116. doi: 10.1080/20013078.2019.1578116. eCollection 2019.

Authors

Eline P Hansen¹, Bastian Fromm^{2

3}, Sidsel D Andersen⁴, Antonio Marcilla^{5

6}, Kasper L Andersen¹, Anne Borup⁴, Andrew R Williams¹, Aaron R Jex^{7

8}, Robin B Gasser⁷, Neil D Young⁷, Ross S Hall⁷, Allan Stensballe^{9

10}, Vladimir Ovchinnikov¹¹, Yan Yan¹², Merete Fredholm¹, Stig M Thamsborg¹, Peter Nejsum^{4

7}

Affiliations

¹ Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
³ Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
⁴ Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
⁵ Departament de Farmàcia Ii Tecnologia Farmacéutica i Parasitologia, Universitat de Valéncia, València, Spain.
⁶ Joint Unit on Endocrinology, Nutrition and Clinical Dietetics, Instituto de Investigación Sanitaria-La Fe Valencia, València, Spain.
⁷ Population Health and Immunity Division, The Walter and Eliza Hall Institute, Melbourne, Australia.
⁸ Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Melbourne, Australia.
⁹ Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
¹⁰ Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
¹¹ Department of Human and Animal Genetics, The Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
¹² Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark.

Abstract

The prevalent porcine helminth, Ascaris suum, compromises pig health and reduces farm productivity worldwide. The closely related human parasite, A. lumbricoides, infects more than 800 million people representing a disease burden of 1.31 million disability-adjusted life years. The infections are often chronic in nature, and the parasites have a profound ability to modulate their hosts' immune responses. This study provides the first in-depth characterisation of extracellular vesicles (EVs) from different developmental stages and body parts of A. suum and proposes the role of these vesicles in the host-parasite interplay. The release of EVs from the third- (L3) and fourth-stage (L4) larvae and adults was demonstrated by transmission electron microscopy (TEM), and sequencing of EV-derived RNA identified a number of microRNAs (miRNAs) and transcripts of potential host immune targets, such as IL-13, IL-25 and IL-33, were identified. Furthermore, proteomics of EVs identified several proteins with immunomodulatory properties and other proteins previously shown to be associated with parasite EVs. Taken together, these results suggest that A. suum EVs and their cargo may play a role in host-parasite interactions. This knowledge may pave the way to novel strategies for helminth infection control and knowledge of their immune modulatory potential.

Keywords: Ascaris suum; extracellular vesicles; host–parasite interactions; immunity; miRNA; proteomics.

Grants and funding

University of Copenhagen, Direktør Ejnar Jonasson kaldet Johnsen og hustrus mindelegat and the Independent Research Fund Denmark (DFF-6111-00521) are acknowledged for funding the project. BF has been supported by the SouthEastern Norway Regional Health Authority (Grant No. 2014041). AM is supported by the Conselleria d’Educació, Cultura i Esports, Generalitat Valenciana (Valencia, Spain) and REDIEX (Spain). AR Jex is a Career Development – Level 2 Fellow of the Australian National Health and Medical Research Council (APP1126395). ND Young is a Career Development Research Fellow of National Health and Medical Research, Australia. V.Y. Ovchinnikov received funding from the Russian Science Foundation grant number 18-15-00098.The Danish National Mass Spectrometry Platform for Functional Proteomics (PRO-MS), The Obel Family Foundation and the Svend Andersen Foundation are acknowledged for grants to the analytical platform enabling parts of this study.