Related Experiment Video

Updated: Jan 31, 2026

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
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High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes

Published on: March 24, 2015

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A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in

Gillian Dunphy1, Irene Adán-Barrientos2, Irene Fernández-Delgado3

  • 1Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.

Immunity
|January 29, 2026
PubMed

Insights

Cytosolic nucleic acid sensing, via interferon-alpha/beta receptor (IFNAR) signaling, enhances macrophage efferocytosis by altering mitochondrial function and limiting inflammation. This pathway boosts efferocytosis while controlling interferon-stimulated gene induction for inflammation resolution.

Area of Science:

  • Immunology
  • Cellular Metabolism
  • Molecular Biology

Background:

  • Macrophage metabolic reprogramming is crucial for immune cell function.
  • Cytosolic nucleic acid sensing influences macrophage metabolism differently than Toll-like receptor stimulation.

Purpose of the Study:

  • To investigate the metabolic and functional consequences of cytosolic nucleic acid sensing in macrophages.
  • To elucidate the role of interferon-alpha/beta receptor (IFNAR) signaling in this process.

Main Methods:

  • Analysis of mitochondrial membrane potential (MMP) and respiration.
  • Assessment of interferon-stimulated gene 15 (ISG15) expression and protein ISGylation.
  • Investigation of mitochondrial protease OMA1 activity and mitochondrial dynamics.
  • Evaluation of endoplasmic reticulum-mitochondria communication and histone acetylation.
  • Assessment of macrophage efferocytic capacity and protection against viral infections.

Main Results:

  • Cytosolic nucleic acid sensing decreased MMP but maintained mitochondrial respiration, dependent on IFNAR signaling.
  • IFNAR signaling induced ISG15 expression and ISGylation of mitochondrial proteins, increasing ATP production and enhancing efferocytosis.
  • The IFNAR-ISG15 pathway activated OMA1, leading to mitochondrial fission and reduced ER-mitochondria communication, which dampened ISG induction.
  • Loss of ISG15 or OMA1 resulted in enhanced ISG induction and histone acetylation, dependent on mitochondrial calcium uptake, conferring protection against viral infections.

Conclusions:

  • IFNAR-ISG15 signaling enhances macrophage efferocytosis by modulating mitochondrial function.
  • This pathway limits excessive ISG induction, promoting the resolution of inflammation.
  • The findings reveal a mechanism balancing immune activation and resolution through macrophage metabolism.
Keywords:
efferocytosisinterferon-stimulated genesmacrophagemetabolismmitochondrial endoplasmic reticulum contactsmitochondrial fissionmitochondrial membrane potentialoxidative phosphorylationtype I interferonviral infection

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