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Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses
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Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses

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Interferon Gamma Reprograms Host Mitochondrial Metabolism through Inhibition of Complex II To Control Intracellular

Forrest Jessop1, Robert Buntyn1, Benjamin Schwarz1

  • 1Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

Infection and Immunity
|November 20, 2019
PubMed

Insights

Interferon gamma (IFN-γ) restricts bacterial growth by altering host mitochondrial metabolism via itaconate production. Targeting mitochondria directly offers a novel therapeutic strategy against infections like tularemia.

Area of Science:

  • Immunology
  • Microbiology
  • Cellular Metabolism

Background:

  • Interferon gamma (IFN-γ) is crucial for controlling cytosolic pathogens.
  • Mechanisms of IFN-γ-mediated pathogen control independent of reactive oxygen/nitrogen species (ROS/RNS) are not fully understood.

Purpose of the Study:

  • To elucidate IFN-γ's non-ROS/RNS dependent mechanisms for controlling *Francisella tularensis* replication.
  • To investigate the role of mitochondrial metabolism in IFN-γ's antimicrobial activity.

Main Methods:

  • Utilized a *Francisella tularensis* infection model in which canonical IFN-γ pathways were dispensable.
  • Assessed the impact of IFN-γ on itaconate production and host mitochondrial function.
  • Evaluated the efficacy of directly targeting mitochondrial complex II.

Main Results:

  • IFN-γ restricts *F. tularensis* replication by inducing itaconate production, impairing mitochondrial function.
  • This IFN-γ-mediated mitochondrial reprogramming is central to bacterial control *in vitro* and *in vivo*.
  • Directly targeting mitochondrial complex II effectively controlled infection, independent of IFN-γ-induced itaconate.

Conclusions:

  • Mitochondrial metabolism reprogramming is a key mechanism for IFN-γ's control of intracellular bacteria.
  • Targeting host mitochondrial metabolism offers a potential therapeutic avenue for infectious diseases, independent of IFN-γ signaling.
Keywords:
Francisella tularensisIFN-γmacrophagesmitochondrial metabolism

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