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FOXO1 Regulates Bacteria-Induced Neutrophil Activity
Guangyu Dong1, Liang Song1,2, Chen Tian1
1Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Frontiers in Immunology
|September 21, 2017
Summary
The transcription factor FOXO1 is crucial for neutrophil mobilization from bone marrow and bacterial clearance during infection. Its activation by bacterial challenge enhances neutrophil chemotaxis and killing of pathogens.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Neutrophils are key innate immune cells vital for combating bacterial infections.
- The transcription factor FOXO1's role in neutrophil response to bacterial challenge requires further elucidation.
Purpose of the Study:
- To investigate the function of FOXO1 in neutrophil response to *Porphyromonas gingivalis* infection.
- To determine FOXO1's regulatory role in neutrophil mobilization, recruitment, chemotaxis, and bacterial killing.
Main Methods:
- Utilized lineage-specific FOXO1 deletion in LyzM.Cre+FOXO1L/L mice and matched controls.
- Performed *in vivo* and *in vitro* experiments to assess neutrophil function.
- Analyzed gene expression, protein interactions, and cellular localization.
Main Results:
- FOXO1 deletion impaired neutrophil mobilization from bone marrow, recruitment to infection sites, and bacterial clearance.
- FOXO1 regulated neutrophil chemotaxis and bacterial killing *in vitro*.
- Bacteria-induced CXCR2 and CD11b expression, essential for neutrophil function, were FOXO1-dependent.
Conclusions:
- FOXO1 activation is essential for neutrophil mobilization and bacterial clearance *in vivo*.
- FOXO1 directly regulates genes critical for neutrophil function, including CXCR2 and CD11b.
- FOXO1 nuclear localization is mediated by Toll-like receptors and influenced by ROS, nitric oxide, and deacetylases.
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