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.read more
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Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA.
Julie Lucifora,Yuchen Xia,Florian Reisinger,Ke Zhang,Daniela Stadler,Xiaoming Cheng,Martin F. Sprinzl,Herwig Koppensteiner,Zuzanna Makowska,Tassilo Volz,Caroline Remouchamps,Wen Min Chou,Wolfgang E. Thasler,Norbert Hüser,David Durantel,T. Jake Liang,Carsten Münk,Markus H. Heim,Jeffrey L. Browning,Emmanuel Dejardin,Maura Dandri,Michael Schindler,Mathias Heikenwalder,Ulrike Protzer +23 more
TL;DR: It is described how interferon-α can induce specific degradation of the nuclear viral DNA without hepatotoxicity and proposed lymphotoxin-β receptor activation as a therapeutic alternative and the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.
Journal ArticleDOI
HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B
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.
Marc Ringelhan,Dominik Pfister,Tracy O'Connor,Eli Pikarsky,Mathias Heikenwalder,Mathias Heikenwalder +5 more
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.
Maurizio Parola,Massimo Pinzani +1 more
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
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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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Dongliang Ge,Jacques Fellay,Alexander J. Thompson,Jason Simon,Kevin V. Shianna,Thomas J. Urban,Erin L. Heinzen,Ping Qiu,Arthur H. Bertelsen,Andrew J. Muir,Mark S. Sulkowski,John G. McHutchison,David Goldstein +12 more
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.