HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/9/2251 |
| _version_ | 1797519893025783808 |
|---|---|
| author | Pelagia Foka Alexios Dimitriadis Eirini Karamichali Emmanouil Kochlios Petros Eliadis Vaia Valiakou John Koskinas Avgi Mamalaki Urania Georgopoulou |
| author_facet | Pelagia Foka Alexios Dimitriadis Eirini Karamichali Emmanouil Kochlios Petros Eliadis Vaia Valiakou John Koskinas Avgi Mamalaki Urania Georgopoulou |
| author_sort | Pelagia Foka |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T07:49:14Z |
| format | Article |
| id | doaj.art-4fc6dd717e694c7599aa86d8528c8ba8 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T07:49:14Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4fc6dd717e694c7599aa86d8528c8ba82023-11-22T12:23:12ZengMDPI AGCells2073-44092021-08-01109225110.3390/cells10092251HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron HomeostasisPelagia Foka0Alexios Dimitriadis1Eirini Karamichali2Emmanouil Kochlios3Petros Eliadis4Vaia Valiakou5John Koskinas6Avgi Mamalaki7Urania Georgopoulou8Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, GreeceMolecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, GreeceMolecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, GreeceMolecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, GreeceMolecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, GreeceMolecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece2nd Department of Internal Medicine, Hippokration Hospital, Medical School of Athens, 11527 Athens, GreeceMolecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, GreeceMolecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, GreeceIron 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.https://www.mdpi.com/2073-4409/10/9/2251ironhepcidinHCVinnate immunitycytokinesco-culture |
| spellingShingle | Pelagia Foka Alexios Dimitriadis Eirini Karamichali Emmanouil Kochlios Petros Eliadis Vaia Valiakou John Koskinas Avgi Mamalaki Urania Georgopoulou HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis Cells iron hepcidin HCV innate immunity cytokines co-culture |
| title | HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis |
| title_full | HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis |
| title_fullStr | HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis |
| title_full_unstemmed | HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis |
| title_short | HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis |
| title_sort | hcv induced immunometabolic crosstalk in a triple cell co culture model capable of simulating systemic iron homeostasis |
| topic | iron hepcidin HCV innate immunity cytokines co-culture |
| url | https://www.mdpi.com/2073-4409/10/9/2251 |
| work_keys_str_mv | AT pelagiafoka hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis AT alexiosdimitriadis hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis AT eirinikaramichali hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis AT emmanouilkochlios hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis AT petroseliadis hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis AT vaiavaliakou hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis AT johnkoskinas hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis AT avgimamalaki hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis AT uraniageorgopoulou hcvinducedimmunometaboliccrosstalkinatriplecellcoculturemodelcapableofsimulatingsystemicironhomeostasis |