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, Jonaset al.
[en] 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.
Research Center/Unit :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
Disciplines :
Immunology & infectious disease
Author, co-author :
Van Breedam, Elise; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
Buyle-Huybrecht, Tamariche; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium
Govaerts, Jonas; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium
Meysman, Pieter; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium ; Adrem Data Lab, Department of Computer Science, University of Antwerp, Antwerp, Belgium ; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, Antwerp, Belgium
Bours, Andrea; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, Antwerp, Belgium
Boeren, Marlies; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium
Di Stefano, Julia; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
Caers, Thalissa; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium
De Reu, Hans; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Flow Cytometry and Cell Sorting Core Facility (FACSUA), Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
Dirkx, Laura; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium
Schippers, Jolien; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
Bartholomeus, Esther; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
Lebrun, Marielle ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Sadzot, Catherine ; Université de Liège - ULiège > Département des sciences de la vie
Rybakowska, Paulina; Department of Genomic Medicine, Centre for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Junta de Andalucía, Parque Tecnológico de la Salud (PTS), Granada, Spain
Alarcón-Riquelme, Marta E; Department of Genomic Medicine, Centre for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Junta de Andalucía, Parque Tecnológico de la Salud (PTS), Granada, Spain
Marañón, Concepción; Department of Genomic Medicine, Centre for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Junta de Andalucía, Parque Tecnológico de la Salud (PTS), Granada, Spain
Laukens, Kris; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium ; Adrem Data Lab, Department of Computer Science, University of Antwerp, Antwerp, Belgium ; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, Antwerp, Belgium
Delputte, Peter; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, Antwerp, Belgium ; Infla-Med, University of Antwerp, Antwerp, Belgium
Ogunjimi, Benson; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium ; Centre for Health Economics Research & Modelling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Department of Paediatrics, Antwerp University Hospital, Antwerp, Belgium
Ponsaerts, Peter; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium ; Flow Cytometry and Cell Sorting Core Facility (FACSUA), Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
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.
This research was funded by the Fund for Scientific Research Flanders (FWO-Vlaanderen) (G067118N granted to KL, PD, and BO; G091518N granted to PP, 1861219N granted to BO and G034721N granted to PP, PD, BO, ML, and CS-D), the Industrial Research Fund (IOF, IOF-SBO 2018 granted to PP) and the ‘Bijzonder Onderzoeksfonds’ (BOF, BOF-GOA 2020 granted to PP) of the University of Antwerp. EB and TB-H are holders of a PhD fellowship that is provided by the University of Antwerp (DOCPRO mandates 36946 and 34720). JS received a PhD fellowship from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813263.This research was funded by the Fund for Scientific Research Flanders (FWO-Vlaanderen) (G067118N granted to KL, PD, and BO; G091518N granted to PP, 1861219N granted to BO and G034721N granted to PP, PD, BO, ML, and CS-D), the Industrial Research Fund (IOF, IOF-SBO 2018 granted to PP) and the ‘Bijzonder Onderzoeksfonds’ (BOF, BOF-GOA 2020 granted to PP) of the University of Antwerp. EB and TB-H are holders of a PhD fellowship that is provided by the University of Antwerp (DOCPRO mandates 36946 and 34720). JS received a PhD fellowship from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813263. Acknowledgments
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