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

Author

Listed:
  • Maciej Czerkies

    (Polish Academy of Sciences)

  • Zbigniew Korwek

    (Polish Academy of Sciences)

  • Wiktor Prus

    (Polish Academy of Sciences)

  • Marek Kochańczyk

    (Polish Academy of Sciences)

  • Joanna Jaruszewicz-Błońska

    (Polish Academy of Sciences)

  • Karolina Tudelska

    (Polish Academy of Sciences)

  • Sławomir Błoński

    (Polish Academy of Sciences)

  • Marek Kimmel

    (Rice University
    Silesian University of Technology)

  • Allan R. Brasier

    (University of Texas Medical Branch)

  • Tomasz Lipniacki

    (Polish Academy of Sciences)

Abstract

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.

Suggested Citation

  • Maciej Czerkies & Zbigniew Korwek & Wiktor Prus & Marek Kochańczyk & Joanna Jaruszewicz-Błońska & Karolina Tudelska & Sławomir Błoński & Marek Kimmel & Allan R. Brasier & Tomasz Lipniacki, 2018. "Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02640-8
    DOI: 10.1038/s41467-017-02640-8
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    Cited by:

    1. Latifa Ait Mahiout & Bogdan Kazmierczak & Vitaly Volpert, 2022. "Viral Infection Spreading and Mutation in Cell Culture," Mathematics, MDPI, vol. 10(2), pages 1-15, January.

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