Peripheral priming induces plastic transcriptomic and proteomic responses in circulating neutrophils required for...

Area of Science:

• Immunology
• Cell Biology
• Infectious Disease

Background:

• Neutrophils are critical immune cells responding to infection, but their functional adaptation in circulation is poorly understood.
• Previous research has been limited by experimental challenges in studying human neutrophils during disease.

Purpose of the Study:

• To investigate the transcriptional and proteomic changes in human and murine neutrophils within the circulation during bacterial infection.
• To elucidate the role of transcriptional plasticity in neutrophil functional reprogramming.

Main Methods:

• Utilized innovative fixation techniques and single-cell-based transcriptomic and proteomic profiling.
• Analyzed neutrophil responses in both human and murine models during steady state and bacterial infection.
• Investigated the impact of blocking de novo RNA synthesis on neutrophil adaptation.

Main Results:

• Identified conserved up-regulation of antimicrobial genes in circulating neutrophils, enhancing pathogen containment.
• Demonstrated TLR4/NF-κB signaling-dependent up-regulation of neutrophil activation markers (e.g., CD177/NB-1) during inflammation.
• Showed that inhibiting RNA synthesis prevents neutrophil adaptation and the up-regulation of effector molecules upon infection.

Conclusions:

• Transcriptional plasticity is a key mechanism for functional neutrophil reprogramming in circulation during acute infection.
• This reprogramming facilitates bacterial containment by up-regulating specific effector molecules.
• Findings provide insights into neutrophil behavior and potential therapeutic targets in infectious diseases.