| Autor: |
Korwek Z; Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research of the Polish Academy of Sciences, Warsaw 02-106, Poland., Czerkies M; Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research of the Polish Academy of Sciences, Warsaw 02-106, Poland., Jaruszewicz-Błońska J; Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research of the Polish Academy of Sciences, Warsaw 02-106, Poland., Prus W; Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research of the Polish Academy of Sciences, Warsaw 02-106, Poland., Kosiuk I; Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research of the Polish Academy of Sciences, Warsaw 02-106, Poland., Kochańczyk M; Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research of the Polish Academy of Sciences, Warsaw 02-106, Poland., Lipniacki T; Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research of the Polish Academy of Sciences, Warsaw 02-106, Poland. |
| Abstrakt: |
Type I interferons (IFNs) are key coordinators of the innate immune response to viral infection, which, through activation of the transcriptional regulators STAT1 and STAT2 (STAT1/2) in bystander cells, induce the expression of IFN-stimulated genes (ISGs). Here, we showed that in cells transfected with poly(I:C), an analog of viral RNA, the transcriptional activity of STAT1/2 was terminated because of depletion of the interferon-β (IFN-β) receptor, IFNAR. Activation of RNase L and PKR, products of two ISGs, not only hindered the replenishment of IFNAR but also suppressed negative regulators of IRF3 and NF-κB, consequently promoting IFNB transcription. We incorporated these findings into a mathematical model of innate immunity. By coupling signaling through the IRF3-NF-κB and STAT1/2 pathways with the activities of RNase L and PKR, the model explains how poly(I:C) switches the transcriptional program from being STAT1/2 induced to being IRF3 and NF-κB induced, which converts IFN-β-responding cells to IFN-β-secreting cells. |
