An apoptosis differentiation programme in human polymorphonuclear leucocytes.

Area of Science:

• Immunology
• Molecular Biology
• Microbiology

Background:

• Human neutrophils (polymorphonuclear leukocytes) are crucial for innate immunity against bacterial pathogens and acute inflammation.
• The molecular mechanisms underlying the resolution of inflammation during human bacterial infections remain largely undefined.

Purpose of the Study:

• To investigate the molecular basis for the termination of neutrophil-mediated inflammation during bacterial infection.
• To gain insight into processes facilitating the resolution of neutrophil-mediated inflammation and bacterial infection using genomics strategies.

Main Methods:

• Genomics strategies were employed to analyze gene expression changes in human neutrophils.
• Studies focused on post-phagocytic processes and the role of reactive oxygen species.

Main Results:

• Global changes in neutrophil gene expression after phagocytosis constitute an apoptosis differentiation program.
• This program represents a transcription-regulated final stage of neutrophil maturation.
• The apoptosis differentiation program influences neutrophil cell fate and pro-inflammatory activity, modulated by reactive oxygen species.

Conclusions:

• A global model of host cell-pathogen interaction is established.
• This model provides fundamental insights into the resolution of human bacterial infections.
• The apoptosis differentiation program is a key mechanism in resolving neutrophil-mediated inflammation.