Abstract:
:Different liver cell types are endowed with immunological properties, including cell-intrinsic innate immune functions that are important to initially control pathogen infections. However, a full landscape of expression and functionality of the innate immune signaling pathways in the major human liver cells is still missing. In order to comparatively characterize these pathways, we purified primary human hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells (LSEC), and Kupffer cells (KC) from human liver resections. We assessed mRNA and protein expression level of the major innate immune sensors, as well as checkpoint-inhibitor ligands in the purified cells, and found Toll-like receptors (TLR), RIG-I-like receptors, as well as several DNA cytosolic sensors to be expressed in the liver microenvironment. Amongst the cells tested, KC were shown to be most broadly active upon stimulation with PRR ligands emphasizing their predominant role in innate immune sensing the liver microenvironment. By KC immortalization, we generated a cell line that retained higher innate immune functionality as compared to THP1 cells, which are routinely used to study monocyte/macrophages functions. Our findings and the establishment of the KC line will help to understand immune mechanisms behind antiviral effects of TLR agonists or checkpoint inhibitors, which are in current preclinical or clinical development.
journal_name
J Innate Immunjournal_title
Journal of innate immunityauthors
Faure-Dupuy S,Vegna S,Aillot L,Dimier L,Esser K,Broxtermann M,Bonnin M,Bendriss-Vermare N,Rivoire M,Passot G,Lesurtel M,Mabrut JY,Ducerf C,Salvetti A,Protzer U,Zoulim F,Durantel D,Lucifora Jdoi
10.1159/000489966subject
Has Abstractpub_date
2018-01-01 00:00:00pages
339-348issue
4eissn
1662-811Xissn
1662-8128pii
000489966journal_volume
10pub_type
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