Related Experiment Video
Updated: Sep 20, 2025
06:50
The Use of Mouse Splenocytes to Assess Pathogen-associated Molecular Pattern Influence on Clock Gene Expression
Published on: July 24, 2018
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A light-regulated circadian timer optimizes neutrophil bactericidal activity to boost daytime immunity
Lucia Yi Du1,2,3, Pramuk Keerthisinghe1,4, Leah Rolland1
1Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Science Immunology
|May 23, 2025
Summary
Neutrophils use a light-responsive internal clock to regulate bacterial killing. Clock gene Per2 controls reactive oxygen species (ROS) production and bacterial clearance, influencing immune responses during infection.
Area of Science:
- Immunology
- Chronobiology
- Molecular Biology
Background:
- The immune system shows strong daily rhythms, impacting bacterial clearance.
- Neutrophils are key in antibacterial defense, but their internal clock mechanisms are unclear.
Purpose of the Study:
- To investigate the role of clock genes in neutrophil function during infection.
- To understand the molecular basis of circadian rhythmicity in neutrophil antibacterial activity.
Main Methods:
- Utilized larval zebrafish models to study neutrophil behavior during infection.
- Employed genetic manipulation to assess the function of clock genes (Per2, Cry1a, BMAL1) in neutrophils.
- Analyzed reactive oxygen species (ROS) production, bacterial killing, and gene expression (hmgb1a).
Main Results:
- Per2 in neutrophils is essential for ROS production and bacterial killing, enhancing hmgb1a expression.
- Neutrophils lacking Cry1a showed increased bactericidal activity and hmgb1a expression.
- A cis-regulatory element with BMAL1 and NF-κB motifs controlled light-phase expression of hmgb1a.
- BMAL1 motif disruption reduced light-dependent priming of bactericidal activity and hmgb1a expression.
Conclusions:
- Identified a cell-intrinsic, light-responsive timer in neutrophils that regulates antibacterial activity.
- Demonstrated that clock genes orchestrate time-of-day variations in the immune response to infection.
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