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Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways

The innate immune system processes pathogen-induced signals into cell fate decisions. How information is turned to decision remains unknown. By combining stochastic mathematical modelling and experimentation, we demonstrate that feedback interactions between the IRF3, NF-κB and STAT pathways lead to...

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Autores principales: Czerkies, Maciej, Korwek, Zbigniew, Prus, Wiktor, Kochańczyk, Marek, Jaruszewicz-Błońska, Joanna, Tudelska, Karolina, Błoński, Sławomir, Kimmel, Marek, Brasier, Allan R., Lipniacki, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799375/
https://www.ncbi.nlm.nih.gov/pubmed/29402958
http://dx.doi.org/10.1038/s41467-017-02640-8
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author Czerkies, Maciej
Korwek, Zbigniew
Prus, Wiktor
Kochańczyk, Marek
Jaruszewicz-Błońska, Joanna
Tudelska, Karolina
Błoński, Sławomir
Kimmel, Marek
Brasier, Allan R.
Lipniacki, Tomasz
author_facet Czerkies, Maciej
Korwek, Zbigniew
Prus, Wiktor
Kochańczyk, Marek
Jaruszewicz-Błońska, Joanna
Tudelska, Karolina
Błoński, Sławomir
Kimmel, Marek
Brasier, Allan R.
Lipniacki, Tomasz
author_sort Czerkies, Maciej
collection PubMed
description The innate immune system processes pathogen-induced signals into cell fate decisions. How information is turned to decision remains unknown. By combining stochastic mathematical modelling and experimentation, we demonstrate that feedback interactions between the IRF3, NF-κB and STAT pathways lead to switch-like responses to a viral analogue, poly(I:C), in contrast to pulse-like responses to bacterial LPS. Poly(I:C) activates both IRF3 and NF-κB, a requirement for induction of IFNβ expression. Autocrine IFNβ initiates a JAK/STAT-mediated positive-feedback stabilising nuclear IRF3 and NF-κB in first responder cells. Paracrine IFNβ, in turn, sensitises second responder cells through a JAK/STAT-mediated positive feedforward pathway that upregulates the positive-feedback components: RIG-I, PKR and OAS1A. In these sensitised cells, the ‘live-or-die’ decision phase following poly(I:C) exposure is shorter—they rapidly produce antiviral responses and commit to apoptosis. The interlinked positive feedback and feedforward signalling is key for coordinating cell fate decisions in cellular populations restricting pathogen spread.
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spelling pubmed-57993752018-02-08 Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways Czerkies, Maciej Korwek, Zbigniew Prus, Wiktor Kochańczyk, Marek Jaruszewicz-Błońska, Joanna Tudelska, Karolina Błoński, Sławomir Kimmel, Marek Brasier, Allan R. Lipniacki, Tomasz Nat Commun Article The innate immune system processes pathogen-induced signals into cell fate decisions. How information is turned to decision remains unknown. By combining stochastic mathematical modelling and experimentation, we demonstrate that feedback interactions between the IRF3, NF-κB and STAT pathways lead to switch-like responses to a viral analogue, poly(I:C), in contrast to pulse-like responses to bacterial LPS. Poly(I:C) activates both IRF3 and NF-κB, a requirement for induction of IFNβ expression. Autocrine IFNβ initiates a JAK/STAT-mediated positive-feedback stabilising nuclear IRF3 and NF-κB in first responder cells. Paracrine IFNβ, in turn, sensitises second responder cells through a JAK/STAT-mediated positive feedforward pathway that upregulates the positive-feedback components: RIG-I, PKR and OAS1A. In these sensitised cells, the ‘live-or-die’ decision phase following poly(I:C) exposure is shorter—they rapidly produce antiviral responses and commit to apoptosis. The interlinked positive feedback and feedforward signalling is key for coordinating cell fate decisions in cellular populations restricting pathogen spread. Nature Publishing Group UK 2018-02-05 /pmc/articles/PMC5799375/ /pubmed/29402958 http://dx.doi.org/10.1038/s41467-017-02640-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Czerkies, Maciej
Korwek, Zbigniew
Prus, Wiktor
Kochańczyk, Marek
Jaruszewicz-Błońska, Joanna
Tudelska, Karolina
Błoński, Sławomir
Kimmel, Marek
Brasier, Allan R.
Lipniacki, Tomasz
Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways
title Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways
title_full Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways
title_fullStr Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways
title_full_unstemmed Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways
title_short Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways
title_sort cell fate in antiviral response arises in the crosstalk of irf, nf-κb and jak/stat pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799375/
https://www.ncbi.nlm.nih.gov/pubmed/29402958
http://dx.doi.org/10.1038/s41467-017-02640-8
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