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Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model

With Varicella-Zoster Virus (VZV) being an exclusive human pathogen, human induced pluripotent stem cell (hiPSC)-derived neural cell culture models are an emerging tool to investigate VZV neuro-immune interactions. Using a compartmentalized hiPSC-derived neuronal model allowing axonal VZV infection,...

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Autores principales: Van Breedam, Elise, Buyle-Huybrecht, Tamariche, Govaerts, Jonas, Meysman, Pieter, Bours, Andrea, Boeren, Marlies, Di Stefano, Julia, Caers, Thalissa, De Reu, Hans, Dirkx, Laura, Schippers, Jolien, Bartholomeus, Esther, Lebrun, Marielle, Sadzot-Delvaux, Catherine, Rybakowska, Paulina, Alarcón-Riquelme, Marta E., Marañón, Concepción, Laukens, Kris, Delputte, Peter, Ogunjimi, Benson, Ponsaerts, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241998/
https://www.ncbi.nlm.nih.gov/pubmed/37287975
http://dx.doi.org/10.3389/fimmu.2023.1177245
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author Van Breedam, Elise
Buyle-Huybrecht, Tamariche
Govaerts, Jonas
Meysman, Pieter
Bours, Andrea
Boeren, Marlies
Di Stefano, Julia
Caers, Thalissa
De Reu, Hans
Dirkx, Laura
Schippers, Jolien
Bartholomeus, Esther
Lebrun, Marielle
Sadzot-Delvaux, Catherine
Rybakowska, Paulina
Alarcón-Riquelme, Marta E.
Marañón, Concepción
Laukens, Kris
Delputte, Peter
Ogunjimi, Benson
Ponsaerts, Peter
author_facet Van Breedam, Elise
Buyle-Huybrecht, Tamariche
Govaerts, Jonas
Meysman, Pieter
Bours, Andrea
Boeren, Marlies
Di Stefano, Julia
Caers, Thalissa
De Reu, Hans
Dirkx, Laura
Schippers, Jolien
Bartholomeus, Esther
Lebrun, Marielle
Sadzot-Delvaux, Catherine
Rybakowska, Paulina
Alarcón-Riquelme, Marta E.
Marañón, Concepción
Laukens, Kris
Delputte, Peter
Ogunjimi, Benson
Ponsaerts, Peter
author_sort Van Breedam, Elise
collection PubMed
description With Varicella-Zoster Virus (VZV) being an exclusive human pathogen, human induced pluripotent stem cell (hiPSC)-derived neural cell culture models are an emerging tool to investigate VZV neuro-immune interactions. Using a compartmentalized hiPSC-derived neuronal model allowing axonal VZV infection, we previously demonstrated that paracrine interferon (IFN)-α2 signalling is required to activate a broad spectrum of interferon-stimulated genes able to counteract a productive VZV infection in hiPSC-neurons. In this new study, we now investigated whether innate immune signalling by VZV-challenged macrophages was able to orchestrate an antiviral immune response in VZV-infected hiPSC-neurons. In order to establish an isogenic hiPSC-neuron/hiPSC-macrophage co-culture model, hiPSC-macrophages were generated and characterised for phenotype, gene expression, cytokine production and phagocytic capacity. Even though immunological competence of hiPSC-macrophages was shown following stimulation with the poly(dA:dT) or treatment with IFN-α2, hiPSC-macrophages in co-culture with VZV-infected hiPSC-neurons were unable to mount an antiviral immune response capable of suppressing a productive neuronal VZV infection. Subsequently, a comprehensive RNA-Seq analysis confirmed the lack of strong immune responsiveness by hiPSC-neurons and hiPSC-macrophages upon, respectively, VZV infection or challenge. This may suggest the need of other cell types, like T-cells or other innate immune cells, to (co-)orchestrate an efficient antiviral immune response against VZV-infected neurons.
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spelling pubmed-102419982023-06-07 Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model Van Breedam, Elise Buyle-Huybrecht, Tamariche Govaerts, Jonas Meysman, Pieter Bours, Andrea Boeren, Marlies Di Stefano, Julia Caers, Thalissa De Reu, Hans Dirkx, Laura Schippers, Jolien Bartholomeus, Esther Lebrun, Marielle Sadzot-Delvaux, Catherine Rybakowska, Paulina Alarcón-Riquelme, Marta E. Marañón, Concepción Laukens, Kris Delputte, Peter Ogunjimi, Benson Ponsaerts, Peter Front Immunol Immunology With Varicella-Zoster Virus (VZV) being an exclusive human pathogen, human induced pluripotent stem cell (hiPSC)-derived neural cell culture models are an emerging tool to investigate VZV neuro-immune interactions. Using a compartmentalized hiPSC-derived neuronal model allowing axonal VZV infection, we previously demonstrated that paracrine interferon (IFN)-α2 signalling is required to activate a broad spectrum of interferon-stimulated genes able to counteract a productive VZV infection in hiPSC-neurons. In this new study, we now investigated whether innate immune signalling by VZV-challenged macrophages was able to orchestrate an antiviral immune response in VZV-infected hiPSC-neurons. In order to establish an isogenic hiPSC-neuron/hiPSC-macrophage co-culture model, hiPSC-macrophages were generated and characterised for phenotype, gene expression, cytokine production and phagocytic capacity. Even though immunological competence of hiPSC-macrophages was shown following stimulation with the poly(dA:dT) or treatment with IFN-α2, hiPSC-macrophages in co-culture with VZV-infected hiPSC-neurons were unable to mount an antiviral immune response capable of suppressing a productive neuronal VZV infection. Subsequently, a comprehensive RNA-Seq analysis confirmed the lack of strong immune responsiveness by hiPSC-neurons and hiPSC-macrophages upon, respectively, VZV infection or challenge. This may suggest the need of other cell types, like T-cells or other innate immune cells, to (co-)orchestrate an efficient antiviral immune response against VZV-infected neurons. Frontiers Media S.A. 2023-05-23 /pmc/articles/PMC10241998/ /pubmed/37287975 http://dx.doi.org/10.3389/fimmu.2023.1177245 Text en Copyright © 2023 Van Breedam, Buyle-Huybrecht, Govaerts, Meysman, Bours, Boeren, Di Stefano, Caers, De Reu, Dirkx, Schippers, Bartholomeus, Lebrun, Sadzot-Delvaux, Rybakowska, Alarcón-Riquelme, Marañón, Laukens, Delputte, Ogunjimi and Ponsaerts https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Van Breedam, Elise
Buyle-Huybrecht, Tamariche
Govaerts, Jonas
Meysman, Pieter
Bours, Andrea
Boeren, Marlies
Di Stefano, Julia
Caers, Thalissa
De Reu, Hans
Dirkx, Laura
Schippers, Jolien
Bartholomeus, Esther
Lebrun, Marielle
Sadzot-Delvaux, Catherine
Rybakowska, Paulina
Alarcón-Riquelme, Marta E.
Marañón, Concepción
Laukens, Kris
Delputte, Peter
Ogunjimi, Benson
Ponsaerts, Peter
Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model
title Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model
title_full Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model
title_fullStr Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model
title_full_unstemmed Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model
title_short Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model
title_sort lack of strong innate immune reactivity renders macrophages alone unable to control productive varicella-zoster virus infection in an isogenic human ipsc-derived neuronal co-culture model
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241998/
https://www.ncbi.nlm.nih.gov/pubmed/37287975
http://dx.doi.org/10.3389/fimmu.2023.1177245
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