Hepatitis C Virus Stimulates Murine CD8α-Like Dendritic Cells to Produce Type I Interferon in a TRIF-Dependent Manner.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Detje, Claudia N
MetadataShow full item record
AbstractHepatitis C virus (HCV) induces interferon (IFN) stimulated genes in the liver despite of distinct innate immune evasion mechanisms, suggesting that beyond HCV infected cells other cell types contribute to innate immune activation. Upon coculture with HCV replicating cells, human CD141+ myeloid dendritic cells (DC) produce type III IFN, whereas plasmacytoid dendritic cells (pDC) mount type I IFN responses. Due to limitations in the genetic manipulation of primary human DCs, we explored HCV mediated stimulation of murine DC subsets. Coculture of HCV RNA transfected human or murine hepatoma cells with murine bone marrow-derived DC cultures revealed that only Flt3-L DC cultures, but not GM-CSF DC cultures responded with IFN production. Cells transfected with full length or subgenomic viral RNA stimulated IFN release indicating that infectious virus particle formation is not essential in this process. Use of differentiated DC from mice with genetic lesions in innate immune signalling showed that IFN secretion by HCV-stimulated murine DC was independent of MyD88 and CARDIF, but dependent on TRIF and IFNAR signalling. Separating Flt3-L DC cultures into pDC and conventional CD11b-like and CD8α-like DC revealed that the CD8α-like DC, homologous to the human CD141+ DC, release interferon upon stimulation by HCV replicating cells. In contrast, the other cell types and in particular the pDC did not. Injection of human HCV subgenomic replicon cells into IFN-β reporter mice confirmed the interferon induction upon HCV replication in vivo. These results indicate that HCV-replicating cells stimulate IFN secretion from murine CD8α-like DC independent of infectious virus production. Thus, this work defines basic principles of viral recognition by murine DC populations. Moreover, this model should be useful to explore the interaction between dendritic cells during HCV replication and to define how viral signatures are delivered to and recognized by immune cells to trigger IFN release.
CitationHepatitis C Virus Stimulates Murine CD8α-Like Dendritic Cells to Produce Type I Interferon in a TRIF-Dependent Manner. 2016, 12 (7):e1005736 PLoS Pathog.
AffiliationTwincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- IPS-1 is essential for type III IFN production by hepatocytes and dendritic cells in response to hepatitis C virus infection.
- Authors: Okamoto M, Oshiumi H, Azuma M, Kato N, Matsumoto M, Seya T
- Issue date: 2014 Mar 15
- IFN-γ production by human natural killer cells in response to HCV-infected hepatoma cells is dependent on accessory cells.
- Authors: Zhang S, Saha B, Kodys K, Szabo G
- Issue date: 2013 Sep
- Efficient virus assembly, but not infectivity, determines the magnitude of hepatitis C virus-induced interferon alpha responses of plasmacytoid dendritic cells.
- Authors: Grabski E, Wappler I, Pfaender S, Steinmann E, Haid S, Dzionek A, Pietschmann T, Kalinke U
- Issue date: 2015 Mar
- Monitoring of Interferon Response Triggered by Cells Infected by Hepatitis C Virus or Other Viruses Upon Cell-Cell Contact.
- Authors: Coléon S, Assil S, Dreux M
- Issue date: 2019
- Vesicular stomatitis virus M protein mutant stimulates maturation of Toll-like receptor 7 (TLR7)-positive dendritic cells through TLR-dependent and -independent mechanisms.
- Authors: Ahmed M, Mitchell LM, Puckett S, Brzoza-Lewis KL, Lyles DS, Hiltbold EM
- Issue date: 2009 Apr