Activating transcription factor 3 involved in Pseudomonas aeruginosa PAO1-induced macrophage senescence

Area of Science:

• Immunology
• Cellular Biology
• Pathogen-Host Interactions

Background:

• Pseudomonas aeruginosa (PA) is a common cause of hospital-acquired infections in critically ill patients.
• PA infection induces macrophage senescence, a state of irreversible cell cycle arrest.
• Activating transcription factor 3 (ATF3), responsive to oxidative stress, is investigated for its role in this senescence process.

Purpose of the Study:

• To investigate the role of ATF3 in PA-induced macrophage senescence.
• To determine how ATF3 expression influences macrophage response to PA infection.
• To elucidate the molecular mechanisms by which ATF3 modulates macrophage senescence and function.

Main Methods:

• Macrophage infection model using Pseudomonas aeruginosa PAO1.
• Manipulation of ATF3 expression (knockdown and overexpression) in macrophages.
• Assessment of macrophage senescence markers, reactive oxygen species (ROS) production, phagocytic capacity, and NF-κB signaling pathway activation (p65 translocation and phosphorylation).

Main Results:

• ATF3 expression increased with PAO1 infection duration and bacterial load.
• ATF3 knockdown exacerbated PA-induced macrophage senescence and increased ROS production.
• ATF3 overexpression partially inhibited PA-induced macrophage senescence.
• ATF3 modulated NF-κB p65 translocation and phosphorylation, affecting downstream cytokine production (IL-6, TNFα, IL-10).
• Phagocytic capacity of macrophages was altered by ATF3 manipulation.

Conclusions:

• ATF3 negatively regulates NF-κB translocation and activation, thereby participating in the control of PA-induced macrophage senescence.
• ATF3 influences macrophage-related host defense mechanisms during infection, potentially through modulation of oxidative stress and inflammation.