Type I interferon receptor signaling delays Kupffer cell replenishment during acute fulminant viral hepatitis.
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
MetadataShow full item record
AbstractVirus-induced fulminant hepatitis is a major cause of acute liver failure. During acute viral hepatitis the impact of type I interferon (IFN-I) on myeloid cells, including liver-resident Kupffer cells (KC), is only partially understood. Herein, we dissected the impact of locally induced IFN-I responses on myeloid cell function and hepatocytes during acute liver inflammation. Two different DNA-encoded viruses, vaccinia virus (VACV) and murine cytomegalovirus (MCMV), were studied. In vivo imaging was applied to visualize local IFN-β induction and IFN-I receptor (IFNAR) triggering in VACV-infected reporter mice. Furthermore, mice with a cell type-selective IFNAR ablation were analyzed to dissect the role of IFNAR signaling in myeloid cells and hepatocytes. Experiments with Cx3cr1 VACV infection induced local IFN-β responses, which lead to IFNAR signaling primarily within the liver. IFNAR triggering was needed to control the infection and prevent fulminant hepatitis. The severity of liver inflammation was independent of IFNAR triggering of hepatocytes, whereas IFNAR triggering of myeloid cells protected from excessive inflammation. Upon VACV or MCMV infection KC disappeared, whereas infiltrating monocytes differentiated to KC afterwards. During IFNAR triggering such replenished monocyte-derived KC comprised more IFNAR-deficient than -competent cells in mixed bone marrow chimeric mice, whereas after the decline of IFNAR triggering both subsets showed an even distribution. Upon VACV infection IFNAR triggering of myeloid cells, but not of hepatocytes, critically modulates acute viral hepatitis. During infection with DNA-encoded viruses IFNAR triggering of liver-infiltrating blood monocytes delays the development of monocyte-derived KC, pointing towards new therapeutic strategies for acute viral hepatitis.
AffiliationTWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 United States
- Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice.
- Authors: Koestner W, Spanier J, Klause T, Tegtmeyer PK, Becker J, Herder V, Borst K, Todt D, Lienenklaus S, Gerhauser I, Detje CN, Geffers R, Langereis MA, Vondran FWR, Yuan Q, van Kuppeveld FJM, Ott M, Staeheli P, Steinmann E, Baumgärtner W, Wacker F, Kalinke U
- Issue date: 2018 Aug
- In Vivo Conditions Enable IFNAR-Independent Type I Interferon Production by Peritoneal CD11b+ Cells upon Thogoto Virus Infection.
- Authors: Kochs G, Anzaghe M, Kronhart S, Wagner V, Gogesch P, Scheu S, Lienenklaus S, Waibler Z
- Issue date: 2016 Oct 15
- Type 1 interferon-induced IL-7 maintains CD8+ T-cell responses and homeostasis by suppressing PD-1 expression in viral hepatitis.
- Authors: Hou L, Jie Z, Liang Y, Desai M, Soong L, Sun J
- Issue date: 2015 Mar
- Alpha/Beta Interferon (IFN-α/β) Signaling in Astrocytes Mediates Protection against Viral Encephalomyelitis and Regulates IFN-γ-Dependent Responses.
- Authors: Hwang M, Bergmann CC
- Issue date: 2018 May 15
- Differential Innate Immune Signaling in Macrophages by Wild-Type Vaccinia Mature Virus and a Mutant Virus with a Deletion of the A26 Protein.
- Authors: Kasani SK, Cheng HY, Yeh KH, Chang SJ, Hsu PW, Tung SY, Liang CT, Chang W
- Issue date: 2017 Sep 15