Related Experiment Video

Updated: Dec 12, 2025

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
06:40

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice

Published on: February 9, 2014

28.9K

Inhibition of mitophagy drives macrophage activation and antibacterial defense during sepsis

Danish Patoli1,2, Franck Mignotte1,2, Valérie Deckert1,2

  • 1Université de Bourgogne Franche-Comté (UBFC), UMR 1231, INSERM/AgroSup Dijon/Université de Bourgogne, Dijon, France.

The Journal of Clinical Investigation
|August 8, 2020
PubMed

Insights

Inhibiting mitophagy in macrophages activates these cells to fight infection, improving survival in sepsis models. This mechanism is also observed in human sepsis patients, suggesting a therapeutic target.

Area of Science:

  • Immunology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • Mitochondria are crucial for innate and adaptive immunity.
  • Mitophagy, the process of clearing damaged mitochondria, is vital for cell homeostasis, but its role in macrophage function and host defense requires further investigation.

Purpose of the Study:

  • To investigate the role of mitophagy in macrophage activation and host defense during infection.
  • To determine the mechanisms by which mitophagy influences macrophage function and sepsis outcomes.

Main Methods:

  • Utilized lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) to inhibit mitophagy in macrophages.
  • Investigated the role of PINK1, STAT1, and inflammatory caspases (1 and 11) in mitophagy regulation.
  • Assessed macrophage activation, mitochondrial reactive oxygen species (ROS), and bacterial clearance in a murine model of polymicrobial infection (cecal ligature and puncture).
  • Analyzed mitophagy levels in blood monocytes from critically ill patients with sepsis.

Main Results:

  • LPS and IFN-γ inhibited PINK1-dependent mitophagy via STAT1-dependent activation of caspases 1 and 11.
  • Mitophagy inhibition promoted classical macrophage activation in a mitochondrial ROS-dependent manner, enhancing bacterial clearance and survival in a sepsis model.
  • Pharmacological inhibition of mitophagy or using PINK1-deficient bone marrow improved sepsis outcomes.
  • Mitochondrial uncouplers that promote mitophagy reversed macrophage activation and led to immunoparalysis.
  • Mitophagy was found to be inhibited in blood monocytes of sepsis patients compared to nonseptic individuals.

Conclusions:

  • Inhibition of mitophagy is a physiological mechanism that activates myeloid cells, contributing to host defense.
  • This mitophagy inhibition enhances bactericidal activity and improves survival rates in sepsis.
  • The findings suggest that modulating mitophagy could be a therapeutic strategy for sepsis and other inflammatory conditions.
Keywords:
InflammationInnate immunityMacrophagesMetabolismMitochondria

More Related Videos

Assessment of Antibody-based Drugs Effects on Murine Bone Marrow and Peritoneal Macrophage Activation10:35

Assessment of Antibody-based Drugs Effects on Murine Bone Marrow and Peritoneal Macrophage Activation

Published on: December 26, 2017

8.5K
High Throughput Fluorometric Technique for Assessment of Macrophage Phagocytosis and Actin Polymerization09:22

High Throughput Fluorometric Technique for Assessment of Macrophage Phagocytosis and Actin Polymerization

Published on: November 27, 2014

15.1K

Related Concept Videos

Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
2.4K
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
7.6K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
4.6K
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
363
Antimicrobial Proteins01:23

Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
12.7K