Human non-parenchymal liver cells produce type I and type III interferons in response to poly I:C, thereby mediating an antiviral state against HCV

2014 ◽  
Vol 52 (01) ◽  
Author(s):  
M Lutterbeck ◽  
R Broering ◽  
K Kleinehr ◽  
A Paul ◽  
G Gerken ◽  
...  
Keyword(s):  
Liver Cells ◽  
Poly I:C ◽  
Type I ◽  
Antiviral State ◽  
Type Iii ◽  
Parenchymal Liver

scholarly journals The Specifics of the Stromal and Parenchymal Liver Components of 0–6-month-old Dead Children from HIV-monoinfected Mothers

2020 ◽  
Vol 8 (B) ◽  
pp. 495-500
Author(s):  
Sergiy O. Sherstiuk ◽  
Stanislav I. Panov ◽  
Igor V. Belozorov ◽  
Tetiana I. Liadova ◽  
Oleksij I. Tsivenko
Keyword(s):  
Bile Ducts ◽  
Collagen Type ◽  
Morphometric Parameters ◽  
Type I ◽  
Type Iii ◽  
Type Iv ◽  
Parenchymal Liver ◽  
Morphometric Investigation ◽  
Stromal Component ◽  
Portal Tracts

OBJECTIVE: The objective of the study was to determine the specifics of the stromal and parenchymal liver components of 0–6-month-old children from HIV-monoinfected mothers. METHODS: The morphometric investigation included 84 liver tissue biopsies of 0–6-month-old dead children from HIV-monoinfected mothers. All morphometric parameters of the parenchymal and stromal liver components were calculated using the Avtandilov’s microscopic morphometric grid, which was consisted of 100 equidistant points. It was inserted into the microscope’s ocular tube with a total ×200 microscope magnification. The number of points that were found on the corresponding types of parenchymal and stromal liver components was calculated. In every case, it was selected 10 random microscopic areas and then all data were obtained, calculated, and presented as percentages. RESULTS: Morphometric parameters of hepatocytes: Mononuclear hepatocytes – 87.3 ± 6.2% (control – 93.5 ± 7.1), two-nuclear hepatocytes – 12.7 ± 1.3% (control – 6.5 ± 1.2), two-/mononuclear hepatocytes coefficient – 0.14 ± 0.01 (control – 0.06 ± 0.01), and hepatocytes with fat vacuoles – 15.6 ± 1.8% (control – 0.5 ± 0.2). Parenchymal and stromal liver components: Parenchyma – 64.3 ± 2.1% (control – 74.2 ± 1.3), stroma (including blood vessels and bile ducts) – 35.7 ± 1.9% (control – 25.8 ± 1.6), and stroma/parenchyma index – 0.55 ± 0.01 (control – 0.34 ± 0.01). Morphometric parameters of all of the liver components: Hepatocytes – 64.3 ± 3.1% (control – 74.2 ± 4.3), portal tracts – 14.9 ± 1.9% (control – 3.1 ± 0.6), central veins – 9.3 ± 1.3 % (control – 9.3 ± 1.4), sinusoids – 8.8 ± 1.1% (control – 10.5 ± 1.3), and bile ducts – 2.7 ± 0.2% (control – 2.9 ± 0.2). Expression level parameters: Fibronectin – 64.8 ± 4.1% (control – 17.3 ± 2.5), collagen Type I – 13.6 ± 1.7% (control – 9.7 ± 1.9), collagen Type III – 15.3 ± 1.4% (control – 10.1 ± 0.9), and collagen Type IV – 6.8 ± 0.2% (control – 5.9 ± 0.2). CONCLUSIONS: It was established that in the liver of 0–6-month-old dead children from HIV-monoinfected mothers, the parenchymal component of the liver showed the signs of its reduction, increase of regenerative activity of hepatocytes, and fatty degeneration of hepatocytes with a certain sign of reactive steatohepatitis. Furthermore, it was established that the stromal component of the liver of children from HIV-infected mothers showed the signs of its progressive proliferation and collagenization due to increased production and accumulation of fibronectin, Type I, Type III collagens in the stroma of portal tracts and newly formed septa, and the signs of hepatic sinusoid capillarization due to Type IV collagen accumulation in the space of Disse of the hepatic sinusoids.

Poly I:C-stimulated human non-parenchymal liver cells are potent suppressors of hepatitis C virus replication

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
M Werner ◽  
K Lukowski ◽  
A Paul ◽  
G Gerken ◽  
JF Schlaak ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Replication ◽  
Liver Cells ◽  
Poly I:C ◽  
Parenchymal Liver

scholarly journals Type I and Type III Interferons Display Different Dependency on Mitogen-Activated Protein Kinases to Mount an Antiviral State in the Human Gut

2017 ◽  
Vol 8 ◽  
Author(s):  
Kalliopi Pervolaraki ◽  
Megan L. Stanifer ◽  
Stephanie Münchau ◽  
Lynnsey A. Renn ◽  
Dorothee Albrecht ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Type I ◽  
Human Gut ◽  
Mitogen Activated Protein Kinases ◽  
Antiviral State ◽  
Type Iii ◽  
Mitogen Activated Protein

P0705 : Antiviral activity of human non-parenchymal liver cells is restricted to toll-like receptor 3 and involves type I interferons

2015 ◽  
Vol 62 ◽  
pp. S587
Author(s):  
M. Lutterbeck ◽  
S. Driftmann ◽  
K. Kleinehr ◽  
A. Paul ◽  
G. Gerken ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Liver Cells ◽  
Type I Interferons ◽  
Type I ◽  
Toll Like Receptor ◽  
Parenchymal Liver

scholarly journals The morphological specifics of the stromal and parenchymal liver components of 6-12-months old children from hiv-mono-infected mothers

2021 ◽  
Keyword(s):  
Bile Ducts ◽  
Collagen Type ◽  
Morphometric Parameters ◽  
Type I ◽  
Type Iii ◽  
Type Iv ◽  
Parenchymal Liver ◽  
Morphometric Investigation ◽  
Stromal Component ◽  
Portal Tracts

To determine the morphological specifics of the stromal and parenchymal liver components of 6-12-months old children from HIV-mono-infected mothers. Materials and methods. The morphometric investigation included 87 liver tissue biopsies of 6-12-months old dead children from HIV-mono-infected mothers. All morphometric parameters of the parenchymal and stromal liver components were calculated using the Avtandilov`s microscopic morphometric grid, which was consisted of 100 equidistant points. It was inserted into the microscope`s ocular tube with a total × 200 microscope magnification. The number of points that were found on the corresponding types of parenchymal and stromal liver components was calculated. In every case, it was selected 10 random microscopic areas and then all data were obtained, calculated and presented as percentages. Results. Morphometric parameters of hepatocytes: mononuclear hepatocytes – 90.2±7.6 % [control – 93.5±7.1], two-nuclear hepatocytes – 9.8±1.2 % [control – 6.5±1.2], TMHC (two-/mononuclear hepatocytes coefficient) – 0.10±0.02 [control – 0.06±0.01], hepatocytes with fat vacuoles – 19.6±2.1 % [control – 0.5±0.2]. Parenchymal and stromal liver components: parenchyma – 56.1±3.3 % [control – 74.2±4.3], stroma (including blood vessels and bile ducts) – 43.9±3.7 % [control – 25.8±2.6], SPI (stroma/parenchyma index) – 0.78±0.02 [control – 0.34±0.01]. Morphometric parameters of all of the liver components: hepatocytes – 56.1±3.3 % [control – 74.2±4.3], portal tracts – 26.4±2.1 % [control – 3.1±0.6], central veins – 8.1±1.2 % [control – 9.3±1.4], sinusoids – 7.3±1.2 % [control – 10.5±1.3], bile ducts – 2.1±0.1 % [control – 2.9±0.2]. Expression level parameters: fibronectin – 73.2±4.2 % [control – 17.3±2.5], collagen type I – 15.9±1.2 % [control – 9.7±1.9], collagen type III – 20.1±2.6 % [control – 10.1±0.9], collagen type IV – 7.3±0.2 % [control – 5.9±0.2]. Conclusions. It was established, that in the liver of 6-12-months old children from HIV-mono-infected mothers, the parenchymal component of the liver showed the signs of its significant reduction, increase of regenerative activity of hepatocytes, and fatty degeneration of hepatocytes with a certain sign of reactive steatohepatitis. Also, it was established, that the stromal component of the liver of children from HIV-infected mothers showed the signs of its progressive proliferation and collagenization due to increased production and accumulation of fibronectin, type I, type III collagens in the stroma of portal tracts and newly formed septa, and the signs of hepatic sinusoid capillarization due to type IV collagen accumulation in the space of Disse of the hepatic sinusoids.

scholarly journals MicroRNA-122 supports robust innate immunity in hepatocytes by suppressing STAT3 phosphorylation

2018 ◽  
Author(s):  
Hui Xu ◽  
Shi-Jun Xu ◽  
Shu-Juan Xie ◽  
Yin Zhang ◽  
Jian-Hua Yang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Tyrosine Kinases ◽  
Large Scale ◽  
Type I Interferons ◽  
Poly I:C ◽  
Hcv Rna ◽  
Type I ◽  
Type Iii ◽  
Stat3 Phosphorylation ◽  
Potential Strategy

ABSTRACTThe intrinsic innate immunity of hepatocytes is essential for the control of hepatitis viruses and influences the outcome of antiviral therapy. MicroRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and is a central player in liver biology and disease. However, little is known about the role of miR-122 in hepatocyte innate immunity. Herein, we show that restoring miR-122 levels in hepatoma cells markedly increased the activation of both type III and type I interferons (IFNs) in response to hepatitis C virus (HCV) RNA or poly(I:C). We determined that miR-122 promotes IFN production through down-regulating the tyrosine (Tyr705) phosphorylation of STAT3. We show that STAT3 represses IFN activation by inhibiting interferon regulatory factor 1 (IRF1), which is rate-limiting for maximal IFN expression, especially type III IFNs. Through large-scale screening, we identified that miR-122 targets MERTK, FGFR1 and IGF1R, three oncogenic receptor tyrosine kinases that directly promote STAT3 phosphorylation. These findings reveal a previously unknown role for miR-122 in hepatic immunity and indicate a new potential strategy for treating hepatic infections through targeting STAT3.

scholarly journals Control of Hepatitis C Virus Replication in Mouse Liver-Derived Cells by MAVS-Dependent Production of Type I and Type III Interferons

2015 ◽  
Vol 89 (7) ◽  
pp. 3833-3845 ◽  
Author(s):  
Anggakusuma ◽  
Anne Frentzen ◽  
Engin Gürlevik ◽  
Qinggong Yuan ◽  
Eike Steinmann ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mouse Liver ◽  
Liver Cells ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Immunocompetent Mouse ◽  
Type Iii ◽  
Mouse Cells ◽  
Human And Mouse

ABSTRACTHepatitis C virus (HCV) efficiently infects only humans and chimpanzees. Although the detailed mechanisms responsible for this narrow species tropism remain elusive, recent evidence has shown that murine innate immune responses efficiently suppress HCV replication. Therefore, poor adaptation of HCV to evade and/or counteract innate immune responses may prevent HCV replication in mice. The HCV NS3-4A protease cleaves human MAVS, a key cellular adaptor protein required for RIG-I-like receptor (RLR)-dependent innate immune signaling. However, it is unclear if HCV interferes with mouse MAVS function equally well. Moreover, MAVS-dependent signaling events that restrict HCV replication in mouse cells were incompletely defined. Thus, we quantified the ability of HCV NS3-4A to counteract mouse and human MAVS. HCV NS3-4A similarly diminished both human and mouse MAVS-dependent signaling in human and mouse cells. Moreover, replicon-encoded protease cleaved a similar fraction of both MAVS variants. Finally, FLAG-tagged MAVS proteins repressed HCV replication to similar degrees. Depending on MAVS expression, HCV replication in mouse liver cells triggered not only type I but also type III IFNs, which cooperatively repressed HCV replication. Mouse liver cells lacking both type I and III IFN receptors were refractory to MAVS-dependent antiviral effects, indicating that the HCV-induced MAVS-dependent antiviral state depends on both type I and III IFN receptor signaling.IMPORTANCEIn this study, we found that HCV NS3-4A similarly diminished both human and mouse MAVS-dependent signaling in human and mouse cells. Therefore, it is unlikely that ineffective cleavage of mouse MAVSper seprecludes HCV propagation in immunocompetent mouse liver cells. Hence, approaches to reinforce HCV replication in mouse liver cells (e.g., by expression of essential human replication cofactors) should not be thwarted by the poor ability of HCV to counteract MAVS-dependent antiviral signaling. In addition, we show that mouse MAVS induces both type I and type III IFNs, which together control HCV replication. Characterization of type I or type III-dependent interferon-stimulated genes in these cells should help to identify key murine restriction factors that preclude HCV propagation in immunocompetent mouse liver cells.

scholarly journals Phagocytosis of Picornavirus-Infected Cells Induces an RNA-Dependent Antiviral State in Human Dendritic Cells

2008 ◽  
Vol 82 (6) ◽  
pp. 2930-2937 ◽  
Author(s):  
Matthijs Kramer ◽  
Barbara M. Schulte ◽  
Liza W. J. Toonen ◽  
Paola M. Barral ◽  
Paul B. Fisher ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Rna ◽  
Poly I:C ◽  
Type I ◽  
Rna Helicases ◽  
Antiviral State ◽  
Interferon Stimulated Genes ◽  
Cytoplasmic Rna ◽  
Endosomal Acidification ◽  
Infected Cells

ABSTRACT Dendritic cells (DCs) play a central role in instructing antiviral immune responses. DCs, however, can become targeted by different viruses themselves. We recently demonstrated that human DCs can be productively infected with echoviruses (EVs), but not coxsackie B viruses (CVBs), both of which are RNA viruses belonging to the Enterovirus genus of the Picornaviridae family. We now show that phagocytosis of CVB-infected, type I interferon-deficient cells induces an antiviral state in human DCs. Uptake of infected cells increased the expression of the cytoplasmic RNA helicases retinoic acid-inducible gene I and melanoma differentiation-associated gene 5 as well as other interferon-stimulated genes and protected DCs against subsequent infection with EV9. These effects depended on recognition of viral RNA and could be mimicked by exposure to the synthetic double-stranded RNA analogue poly(I:C) but not other Toll-like receptor (TLR) ligands. Blocking endosomal acidification abrogated protection, suggesting a role for TLRs in the acquisition of an antiviral state in DCs. In conclusion, recognition of viral RNA rapidly induces an antiviral state in human DCs. This might provide a mechanism by which DCs protect themselves against viruses when attracted to an environment with ongoing infection.

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