Microplastics modulate neutrophil migration via an ROShistone lactylation positive feedback loop

Area of Science:

• Environmental Toxicology
• Immunology
• Epigenetics

Background:

• Microplastics (MPs) pose significant toxic risks, with known impacts on neutrophil function.
• Real-time visualization and regulatory mechanisms of MP-induced neutrophil migration in vivo remain largely unexplored.

Purpose of the Study:

• To visualize and elucidate the regulatory mechanisms of microplastic-induced neutrophil migration in live organisms.
• To investigate the roles of reactive oxygen species (ROS) and histone lactylation in microplastic immunotoxicity.

Main Methods:

• Zebrafish were exposed to microplastics (MPs).
• Transcriptomic analysis, gene and protein expression analysis (lactylation, cytokines, oxidative stress markers), and in vivo imaging were employed.
• Inhibition of lactate production (2DG) and oxidative stress (Dpi) were used to validate mechanisms.
• Lactylation-specific ChIP-seq and ChIP-qPCR were performed.

Main Results:

• MPs significantly increased neutrophil migration in zebrafish.
• Microplastic exposure upregulated histone lactylation (H3K18la) and ROS levels.
• A positive feedback loop between ROS and lactylation was identified, promoting neutrophil migration.
• Inhibiting lactate production or oxidative stress reversed MP-induced neutrophil migration.

Conclusions:

• This study provides the first real-time in vivo visualization of MP-induced neutrophil migration.
• A novel ROS-lactylation positive feedback loop mechanism driving neutrophil migration under MP exposure was elucidated.
• Findings offer new insights into the immunotoxicity of microplastics.