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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

The transcription factor IRF3 triggers "defensive suicide" necrosis in response to viral and bacterial pathogens

Nelson C Di Paolo1, Konstantin Doronin, Lisa K Baldwin

  • 1Division of Medical Genetics, University of Washington, Seattle, WA 98195, USA.

Cell Reports
|June 18, 2013
PubMed

Insights

Interferon-regulatory factor 3 (IRF3) controls rapid necrotic cell death in macrophages during infection. This IRF3-dependent necrosis acts as an innate immune mechanism protecting against disseminated viral infections.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Molecular pathways governing necrotic cell death are poorly understood, unlike those for apoptotic cell death.
  • Interferon-regulatory factor 3 (IRF3) is a key transcription factor in innate immunity.

Purpose of the Study:

  • To investigate the molecular mechanisms controlling necrotic cell death in macrophages during infection.
  • To determine the role of IRF3 in regulating necrotic cell death and host defense.

Main Methods:

  • In vivo studies using mouse models infected with adenovirus and Listeria monocytogenes.
  • Analysis of necrotic cell death pathways, including IRF3 activation and its downstream transcriptional activity.
  • Assessment of host defense mechanisms in wild-type and genetically deficient mice.

Main Results:

  • Macrophages undergo rapid, proinflammatory necrotic death controlled by IRF3 in response to viral and bacterial infections.
  • IRF3-dependent necrosis occurs independently of known regulators like RIPK3, caspases, STING, and MAVS.
  • While Listeria monocytogenes utilizes necrosis to promote infection, IRF3-dependent necrosis is crucial for controlling adenovirus burden.

Conclusions:

  • IRF3 is a principal regulator of a physiologically controlled necrotic cell death pathway.
  • This IRF3-mediated necrosis serves as an innate immune mechanism for host protection against disseminated viral infections.

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