Fas-associated factor 1 mediates NADPH oxidase-induced reactive oxygen species production and proinflammatory responses in macrophages against Listeria infection
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Updated: Jan 8, 2026
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Published on: April 25, 2025
Tae-Hwan Kim1, Hyun-Cheol Lee1, Jae-Hoon Kim1,2
1College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
Abstract:
Fas-associated factor 1 is a death-promoting protein that induces apoptosis by interacting with the Fas receptor. Until now, FAF1 was reported to interact potentially with diverse proteins and to function as a negative and/or positive regulator of several cellular possesses. However, the role of FAF1 in defense against bacterial infection remains unclear. Here, we show that FAF1 plays a pivotal role in activating NADPH oxidase in macrophages during Listeria monocytogenes infection. Upon infection by L. monocytogenes, FAF1 interacts with p67phox (an activator of the NADPH oxidase complex), thereby facilitating its stabilization and increasing the activity of NADPH oxidase. Consequently, knockdown or ectopic expression of FAF1 had a marked effect on production of ROS, proinflammatory cytokines, and antibacterial activity, in macrophages upon stimulation of TLR2 or after infection with L. monocytogenes. Consistent with this, FAF1gt/gt mice, which are knocked down in FAF1, showed weaker inflammatory responses than wild-type mice; these weaker responses led to increased replication of L. monocytogenes. Collectively, these findings suggest that FAF1 positively regulates NADPH oxidase-mediated ROS production and antibacterial defenses.
Insights
Fas-associated factor 1 (FAF1) activates NADPH oxidase in macrophages, enhancing bacterial defenses against Listeria monocytogenes. This protein is crucial for producing reactive oxygen species and mounting an effective immune response.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Fas-associated factor 1 (FAF1) is known to regulate apoptosis and interact with various proteins.
- The specific role of FAF1 in bacterial infection defense was previously undefined.
Purpose of the Study:
- To investigate the function of FAF1 in macrophage response to Listeria monocytogenes infection.
- To elucidate the mechanism by which FAF1 influences antibacterial activity.
Main Methods:
- Investigated FAF1 interaction with p67phox in macrophages during L. monocytogenes infection.
- Assessed the impact of FAF1 knockdown and overexpression on reactive oxygen species (ROS) and cytokine production.
- Utilized FAF1gt/gt mice to evaluate in vivo inflammatory responses and bacterial load.
Main Results:
- FAF1 directly interacts with p67phox, stabilizing it and enhancing NADPH oxidase activity.
- FAF1 modulation significantly affects ROS production, pro-inflammatory cytokine release, and antibacterial activity in macrophages.
- FAF1gt/gt mice exhibit diminished inflammatory responses and increased L. monocytogenes replication.
Conclusions:
- FAF1 plays a critical role in activating NADPH oxidase-dependent ROS production during bacterial infection.
- FAF1 enhances macrophage antibacterial defenses against Listeria monocytogenes.
- FAF1 is a key positive regulator of innate immunity against bacterial pathogens.
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