Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597522
5. Virus Immunology
Georg Thieme Verlag KG Stuttgart · New York

Macrophage-derived extracellular vesicles mediate a long-lasting innate immune response against hepatitis C virus

C Cai
1   Goethe-Universitätsklinikum Frankfurt, Medizinische Klinik 1, Frankfurt am Main, Germany
,
B Koch
2   Goethe-Universitätsklinikum Frankfurt, Medizinische Klinik 3, Frankfurt am Main, Germany
,
S Akhras
3   Paul-Ehrlich-Institut, Abteilung für Virologie, Langen, Germany
,
E Hildt
3   Paul-Ehrlich-Institut, Abteilung für Virologie, Langen, Germany
,
S Zeuzem
1   Goethe-Universitätsklinikum Frankfurt, Medizinische Klinik 1, Frankfurt am Main, Germany
,
CM Lange
1   Goethe-Universitätsklinikum Frankfurt, Medizinische Klinik 1, Frankfurt am Main, Germany
› Author Affiliations
Further Information
Cai, Chengcong

Publication History

Publication Date:
19 December 2016 (online)

Also available at
 
 

    Background: Interferons play a pivotal role in the first line defense against viral infections. Macrophages are both important producers and responders to type I and II interferons and participate in antiviral immune responses. Yet, the precise role of macrophages in the immune response against hepatitis C virus (HCV) has not been entirely elucidated. In the present study, we therefore aim to further characterize mechanisms of macrophage-mediated antiviral immune responses against hepatitis C virus (HCV).

    Methods: THP-1 cells and monocyte-derived macrophages from human buffy coats were stimulated with type I and II interferons. Whole supernatants and purified extracellular vesicles secreted from interferon-pulsed macrophages were transferred to Huh-7.5 cells harboring subgenomic HCV replicons. HCV replication was quantified by quantitative PCR. Macrophage-derived supernatants and extracellular vesicles were analyzed by cytokine arrays, RNA-sequencing, flow cytometry and electron microscopy.

    Results: Macrophages secrete a variety of cytokines shortly after stimulation with type I and II interferons, which orchestrate a fast but short-lasting antiviral state against HCV. In addition, interferon-pulsed macrophages secrete extracellular vesicles which induce a late, but long-lasting (5 – 7 days) inhibitory effect on HCV replication. Though extracellular vesicles of both THP-1 cells and primary human macrophages exhibit antiviral qualities, they are different with respect to vesicle size and content of extracellular vesicle markers. Preliminary results indicate that long-coding RNAs may mediate the long-lasting antiviral effects of macrophage-derived extracellular vesicles.

    Conclusion: Macrophage-derived extracellular vesicles mediate long-lasting inhibitory effects on HCV replication in vitro, which may bridge the time until efficient adaptive immune responses are established.


    #

    No conflict of interest has been declared by the author(s).

    Cai, Chengcong