Τίτλος:
HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model
Capable of Simulating Systemic Iron Homeostasis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Iron is crucial to the regulation of the host innate immune system and
the outcome of many infections. Hepatitis C virus (HCV), one of the
major viral human pathogens that depends on iron to complete its life
cycle, is highly skilled in evading the immune system. This study
presents the construction and validation of a physiologically relevant
triple-cell co-culture model that was used to investigate the input of
iron in HCV infection and the interplay between HCV, iron, and
determinants of host innate immunity. We recorded the expression
patterns of key proteins of iron homeostasis involved in iron import,
export and storage and examined their relation to the iron regulatory
hormone hepcidin in hepatocytes, enterocytes and macrophages in the
presence and absence of HCV. We then assessed the transcriptional
profiles of pro-inflammatory cytokines Interleukin-6 (IL-6) and
interleukin-15 (IL-15) and anti-inflammatory interleukin-10 (IL-10)
under normal or iron-depleted conditions and determined how these were
affected by infection. Our data suggest the presence of a link between
iron homeostasis and innate immunity unfolding among liver, intestine,
and macrophages, which could participate in the deregulation of innate
immune responses observed in early HCV infection. Coupled with
iron-assisted enhanced viral propagation, such a mechanism may be
important for the establishment of viral persistence and the ensuing
chronic liver disease.
Συγγραφείς:
Foka, Pelagia
Dimitriadis, Alexios
Karamichali, Eirini and
Kochlios, Emmanouil
Eliadis, Petros
Valiakou, Vaia
Koskinas,
John
Mamalaki, Avgi
Georgopoulou, Urania
Περιοδικό:
Cell Stem Cell
Λέξεις-κλειδιά:
iron; hepcidin; HCV; innate immunity; cytokines; co-culture; ferritin;
enterocytes; macrophages
DOI:
10.3390/cells10092251
