Differential induction of interferon stimulated genes between type I and type III interferons is independent of interferon receptor abundance

Pervolaraki, K. et al. (2018) Differential induction of interferon stimulated genes between type I and type III interferons is independent of interferon receptor abundance. PLoS Pathogens, 14(11), e1007420. (doi: 10.1371/journal.ppat.1007420) (PMID:30485383) (PMCID:PMC6287881)

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Abstract

It is currently believed that type I and III interferons (IFNs) have redundant functions. However, the preferential distribution of type III IFN receptor on epithelial cells suggests functional differences at epithelial surfaces. Here, using human intestinal epithelial cells we could show that although both type I and type III IFNs confer an antiviral state to the cells, they do so with distinct kinetics. Type I IFN signaling is characterized by an acute strong induction of interferon stimulated genes (ISGs) and confers fast antiviral protection. On the contrary, the slow acting type III IFN mediated antiviral protection is characterized by a weaker induction of ISGs in a delayed manner compared to type I IFN. Moreover, while transcript profiling revealed that both IFNs induced a similar set of ISGs, their temporal expression strictly depended on the IFNs, thereby leading to unique antiviral environments. Using a combination of data-driven mathematical modeling and experimental validation, we addressed the molecular reason for this differential kinetic of ISG expression. We could demonstrate that these kinetic differences are intrinsic to each signaling pathway and not due to different expression levels of the corresponding IFN receptors. We report that type III IFN is specifically tailored to act in specific cell types not only due to the restriction of its receptor but also by providing target cells with a distinct antiviral environment compared to type I IFN. We propose that this specific environment is key at surfaces that are often challenged with the extracellular environment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McLauchlan, Professor John and Bamford, Dr Connor
Creator Roles:
Bamford, C.Methodology, Writing – review and editing
McLauchlan, J.Methodology
Authors: Pervolaraki, K., Rastgou Talemi, S., Albrecht, D., Bormann, F., Bamford, C., Mendoza, J. L., Garcia, K. C., McLauchlan, J., Höfer, T., Stanifer, M. L., and Boulant, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Published Online:28 November 2018
Copyright Holders:Copyright © 2018 Pervolaraki et al.
First Published:First published in PLoS Pathogens 14(11): e1007420
Publisher Policy:Reproduced under a Creative Commons License

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