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Journal ArticleDOI

Living in the liver: hepatic infections

TLDR
The interplay between pathogens and host factors that promote pathogen elimination and maintain organ integrity or that allow pathogen persistence are described.
Abstract
The liver has vital metabolic and clearance functions that involve the uptake of nutrients, waste products and pathogens from the blood. In addition, its unique immunoregulatory functions mediated by local expression of co-inhibitory receptors and immunosuppressive mediators help to prevent inadvertent organ damage. However, these tolerogenic properties render the liver an attractive target site for pathogens. Although most pathogens that reach the liver via the blood are eliminated or controlled by local innate and adaptive immune responses, some pathogens (such as hepatitis viruses) can escape immune control and persist in hepatocytes, causing substantial morbidity and mortality worldwide. Here, we review our current knowledge of the mechanisms of liver targeting by pathogens and describe the interplay between pathogens and host factors that promote pathogen elimination and maintain organ integrity or that allow pathogen persistence.

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Citations
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Journal ArticleDOI

HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B

Michael Nassal
- 03 Jun 2015 - 
TL;DR: This review aims to summarise current knowledge on ccc DNA molecular biology, to highlight the experimental restrictions that have hitherto hampered faster progress and to discuss cccDNA as target for new, potentially curative therapies of chronic hepatitis B.
Journal ArticleDOI

Liver immunology and its role in inflammation and homeostasis

TL;DR: The changing perception of inflammation and inflammatory mediators in normal liver homeostasis is explored and targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease is proposed.
Journal ArticleDOI

The immunology of hepatocellular carcinoma.

TL;DR: The roles of specific immune cell subsets in chronic liver disease, with a focus on non-alcoholic steatohepatitis and HCC are summarized and the challenges posed by the immunotolerant hepatic environment are discussed.
Journal ArticleDOI

Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues.

TL;DR: This review will analyze the most relevant established and/or emerging pathophysiological issues underlying CLD progression with a focus on the role of critical hepatic cell populations, mechanisms and signaling pathways involved, as they represent potential therapeutic targets to finally analyze selected and relevant clinical issues.
References
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Journal ArticleDOI

Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.

TL;DR: It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).
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Restoring function in exhausted CD8 T cells during chronic viral infection.

TL;DR: In this article, the authors analyzed genes expressed in functionally impaired virus-specific CD8 T cells present in mice chronically infected with lymphocytic choriomeningitis virus (LCMV), and compared these with the gene profile of functional memory CD8T cells.
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Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.

TL;DR: It is reported that a genetic polymorphism near the IL28B gene, encoding interferon-λ-3 (IFN-α-2a) is associated with an approximately twofold change in response to treatment, both among patients of European ancestry and African-Americans.
Journal ArticleDOI

T cell exhaustion

TL;DR: Advances in the molecular delineation of T cell exhaustion are clarifying the underlying causes of this state of differentiation and also suggest promising therapeutic opportunities.
Journal Article

Restoring function in exhausted CD8 T cells during chronic viral infection

TL;DR: It is found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the ‘helpless’ CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load.
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