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High-Frequency Repetitive Magnetic Stimulation Activates Bactericidal Activity of Macrophages via Modulation of
Therese B Deramaudt1, Ahmad Chehaitly1, Théo Charrière1
1U1179 INSERM, END-ICAP, UFR des Sciences de la Santé-Simone Veil, Université de Versailles Saint-Quentin-en-Yvelines, 78180 Montigny-le-Bretonneux, France.
Abstract:
The effects of repetitive magnetic stimulation (rMS) have predominantly been studied in excitable cells, with limited research in non-excitable cells. This study aimed to investigate the impact of rMS on macrophages, which are crucial cells in the innate immune defense. THP-1-derived macrophages subjected to a 5 min session of 10 Hz rMS exhibited increased Nrf2 activation and decreased Keap1 expression. We found that activation of the Nrf2 signaling pathway relied on rMS-induced phosphorylation of p62. Notably, rMS reduced the intracellular survival of Staphylococcus aureus in macrophages. Silencing Nrf2 using siRNA in THP-1-derived macrophages or utilizing Nrf2 knockout in alveolar macrophages abolished this effect. Additionally, rMS attenuated the expression of IL-1β and TNF-α inflammatory genes by S. aureus and inhibited p38 MAPK activation. These findings highlight the capacity of rMS to activate the non-canonical Nrf2 pathway, modulate macrophage function, and enhance the host's defense against bacterial infection.
Insights
Repetitive magnetic stimulation (rMS) activates the Nrf2 pathway in macrophages, enhancing their ability to fight Staphylococcus aureus infections. This immune modulation offers a novel therapeutic approach for bacterial defense.
Area of Science:
- Immunology
- Cell Biology
- Neuroscience
Background:
- Repetitive magnetic stimulation (rMS) effects are primarily studied in excitable cells.
- Limited research exists on rMS impact on non-excitable cells like macrophages.
- Macrophages are key players in innate immune defense.
Purpose of the Study:
- Investigate the effects of rMS on macrophage function.
- Determine if rMS can enhance macrophage defense against bacterial pathogens.
- Explore the underlying molecular mechanisms of rMS in macrophages.
Main Methods:
- THP-1 derived macrophages were subjected to 10 Hz rMS for 5 minutes.
- Nrf2 activation, Keap1 expression, and p62 phosphorylation were analyzed.
- Intracellular survival of Staphylococcus aureus was assessed.
- Nrf2 silencing (siRNA) and knockout macrophages were used to confirm Nrf2 dependency.
- Inflammatory gene expression (IL-1β, TNF-α) and p38 MAPK activation were measured.
Main Results:
- rMS increased Nrf2 activation and decreased Keap1 expression in macrophages.
- Nrf2 pathway activation was dependent on rMS-induced p62 phosphorylation.
- rMS significantly reduced intracellular Staphylococcus aureus survival.
- Nrf2 silencing or knockout abolished the anti-bacterial effect of rMS.
- rMS attenuated S. aureus-induced expression of IL-1β and TNF-α and inhibited p38 MAPK activation.
Conclusions:
- rMS activates the non-canonical Nrf2 pathway in macrophages.
- rMS modulates macrophage function, enhancing host defense against bacterial infections.
- rMS demonstrates potential as a therapeutic strategy for combating bacterial pathogens.
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