Macrophage-derived extracellular vesicles induce long-lasting immunity against Hepatitis C virus which is blunted by Polyunsaturated fatty acids

  • Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. In this study, we aimed to further characterize the role of macrophage-derived EVs in immune responses against hepatitis C virus (HCV) and the potential of polyunsaturated fatty acids (PUFAs) to modulate this modality of innate immunity. To this end, EVs were isolated from interferon-stimulated macrophage cultures or from serum of patients with acute or chronic hepatitis C. EVs were characterized by electron microscopy, flow cytometry, RNA-sequencing, and Western blot analysis. The effect of EVs on replication of HCV was assessed in coculture models. Functional analyses were performed to assess the impact of PUFAs on EV-mediated antiviral immunity. We found that macrophages secreted various cytokines shortly after stimulation with type I and II IFN, which orchestrated a fast but short-lasting antiviral state. This rapid innate immune answer was followed by the production of macrophage-derived EVs, which induced a late, but long-lasting inhibitory effect on HCV replication. Of note, exposure of macrophages to PUFAs, which are important regulators of immune responses, dampened EV-mediated antiviral immune responses. Finally, EVs from patients with hepatitis C exhibited long-lasting antiviral activities during IFN therapy as well. The antiviral effect of EVs from Caucasian and Japanese patients differed, which may be explained by different nutritional uptake of PUFAs. In conclusion, our data indicate that macrophage-derived EVs mediate long-lasting inhibitory effects on HCV replication, which may bridge the time until efficient adaptive immune responses are established, and which can be blunted by PUFAs.

Download full text files

Export metadata

Author:Chengcong Cai, Benjamin Florian KochORCiDGND, Kenichi Morikawa, Goki Suda, Naoya Sakamoto, Sabrina Rüschenbaum, Sami Akhras, Julia DietzORCiDGND, Eberhard HildtORCiDGND, Stefan ZeuzemORCiDGND, Christoph WelschORCiDGND, Christian Michael Lange
Pubmed Id:
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Wenzhe Ho
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/04/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/05/22
Tag:arachidonic acid; exosomes; innate immunity; interferon; omega-3 fatty acids
Issue:Art. 723
Page Number:11
First Page:1
Last Page:11
Copyright: © 2018 Cai, Koch, Morikawa, Suda, Sakamoto, Rueschenbaum, Akhras, Dietz, Hildt, Zeuzem, Welsch and Lange. 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.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0