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
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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