10.3389/fimmu.2018.00723.s001
Chengcong Cai
Chengcong
Cai
Benjamin Koch
Benjamin
Koch
Kenichi Morikawa
Kenichi
Morikawa
Goki Suda
Goki
Suda
Naoya Sakamoto
Naoya
Sakamoto
Sabrina Rueschenbaum
Sabrina
Rueschenbaum
Sami Akhras
Sami
Akhras
Julia Dietz
Julia
Dietz
Eberhard Hildt
Eberhard
Hildt
Stefan Zeuzem
Stefan
Zeuzem
Christoph Welsch
Christoph
Welsch
Christian M. Lange
Christian
M. Lange
Data_Sheet_1.PDF
Frontiers
2018
exosomes
interferon
innate immunity
omega-3 fatty acids
arachidonic acid
2018-04-12 09:53:01
Dataset
https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_PDF/6133286
<p>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.</p>