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

被引：74

作者：

Czerkies, Maciej ^{[1
]}

Korwek, Zbigniew ^{[1
]}

Prus, Wiktor ^{[1
]}

Kochanczyk, Marek ^{[1
]}

Jaruszewicz-Blonska, Joanna ^{[1
]}

Tudelska, Karolina ^{[1
]}

Blonski, Slawomir ^{[1
]}

Kimmel, Marek ^{[2
,3
,4
,5
]}

Brasier, Allan R. ^{[6
]}

Lipniacki, Tomasz ^{[1
]}

机构：

[1] Polish Acad Sci, Inst Fundamental Technol Res, PL-02106 Warsaw, Poland

[2] Rice Univ, Dept Stat, Houston, TX 77005 USA

[3] Rice Univ, Dept Bioengn, Houston, TX 77005 USA

[4] Rice Univ, Program Syst Synthet & Phys Biol, Houston, TX 77005 USA

[5] Silesian Tech Univ, Syst Engn Grp, PL-44100 Gliwice, Poland

[6] Univ Texas Med Branch, Inst Translat Sci, Galveston, TX 77555 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

美国国家科学基金会;

关键词：

DOUBLE-STRANDED-RNA; INDUCIBLE GENE-I; BETA RESPONSE; IFN; EXPRESSION; ACTIVATION; DYNAMICS; RECOGNITION; SUPPRESSOR; INDUCTION;

D O I：

10.1038/s41467-017-02640-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-kappa B 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-kappa B, a requirement for induction of IFN beta expression. Autocrine IFN beta initiates a JAK/STAT-mediated positive-feedback stabilising nuclear IRF3 and NF-kappa B in first responder cells. Paracrine IFN beta, 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.

引用

页数：14

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