Human PSC-Derived Hepatocytes Express Low Levels of Viral Pathogen Recognition Receptors, but Are Capable of Mounting an Effective Innate Immune Response
Autor: | Lena Fischer, Cliona O'Farrelly, Baltasar Lucendo-Villarin, David C. Hay |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cytoplasm Receptor expression Ligands lcsh:Chemistry 0302 clinical medicine Receptor lcsh:QH301-705.5 Spectroscopy metabolic switch Toll-Like Receptors Pattern recognition receptor MDA5 Cell Differentiation General Medicine innate anti-viral immunity Computer Science Applications Cell biology Up-Regulation Receptors Pattern Recognition Receptors Virus 030211 gastroenterology & hepatology hepatocyte-like cells Signal Transduction Induced Pluripotent Stem Cells Endosomes Biology Antiviral Agents Catalysis Article Proinflammatory cytokine Inorganic Chemistry 03 medical and health sciences Downregulation and upregulation stem cells Humans Physical and Theoretical Chemistry Molecular Biology Embryonic Stem Cells Janus Kinases Inflammation Innate immune system Tumor Necrosis Factor-alpha Organic Chemistry Immunity Innate 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Microscopy Fluorescence TLR3 Hepatocytes pattern recognition receptors (PRRs) |
Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 11 Fischer, L, Lucendo Villarin, B, Hay, D & O'Farrelly, C 2020, ' Human PSC-derived hepatocytes express low levels of viral pathogen recognition receptors, but are capable of mounting an effective innate immune response ', International Journal of Molecular Sciences, vol. 21, no. 11, 3831 . https://doi.org/10.3390/ijms21113831 International Journal of Molecular Sciences, Vol 21, Iss 3831, p 3831 (2020) |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms21113831 |
Popis: | Hepatocytes are key players in the innate immune response to liver pathogens but are challenging to study because of inaccessibility and a short half-life. Recent advances in in vitro differentiation of hepatocyte-like cells (HLCs) facilitated studies of hepatocyte&ndash pathogen interactions. Here, we aimed to define the anti-viral innate immune potential of human HLCs with a focus on toll-like receptor (TLR)-expression and the presence of a metabolic switch. We analysed cytoplasmic pattern recognition receptor (PRR)- and endosomal TLR-expression and activity and adaptation of HLCs to an inflammatory environment. We found that transcript levels of retinoic acid inducible gene I (RIG-I), melanoma differentiation antigen 5 (MDA5), and TLR3 became downregulated during differentiation, indicating the acquisition of a more tolerogenic phenotype, as expected in healthy hepatocytes. HLCs responded to activation of RIG-I by producing interferons (IFNs) and IFN-stimulated genes. Despite low-level expression of TLR3, receptor expression was upregulated in an inflammatory environment. TLR3 signalling induced expression of proinflammatory cytokines at the gene level, indicating that several PRRs need to interact for successful innate immune activation. The inflammatory responsiveness of HLCs was accompanied by the downregulation of cytochrome P450 3A and 1A2 activity and decreased serum protein production, showing that the metabolic switch seen in primary hepatocytes during anti-viral responses is also present in HLCs. |
Databáze: | OpenAIRE |
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