{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T21:46:12Z","timestamp":1767908772465,"version":"3.49.0"},"reference-count":81,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003448","name":"General Secretariat for Research and Technology","doi-asserted-by":"publisher","award":["09SYN-12-68"],"award-info":[{"award-number":["09SYN-12-68"]}],"id":[{"id":"10.13039\/501100003448","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003448","name":"General Secretariat for Research and Technology","doi-asserted-by":"publisher","award":["MIS 450598 KRIPIS"],"award-info":[{"award-number":["MIS 450598 KRIPIS"]}],"id":[{"id":"10.13039\/501100003448","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells10092251","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T11:01:37Z","timestamp":1630321297000},"page":"2251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6888-7678","authenticated-orcid":false,"given":"Pelagia","family":"Foka","sequence":"first","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-1423","authenticated-orcid":false,"given":"Alexios","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"Molecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirini","family":"Karamichali","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanouil","family":"Kochlios","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-2449","authenticated-orcid":false,"given":"Petros","family":"Eliadis","sequence":"additional","affiliation":[{"name":"Molecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0956-2344","authenticated-orcid":false,"given":"Vaia","family":"Valiakou","sequence":"additional","affiliation":[{"name":"Molecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Koskinas","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Hippokration Hospital, Medical School of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avgi","family":"Mamalaki","sequence":"additional","affiliation":[{"name":"Molecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2784-3695","authenticated-orcid":false,"given":"Urania","family":"Georgopoulou","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jtemb.2018.03.007","article-title":"Iron and innate antimicrobial immunity-Depriving the pathogen, defending the host","volume":"48","author":"Nairz","year":"2018","journal-title":"J. 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