An apoptosis differentiation programme in human polymorphonuclear leucocytes

S D Kobayashi1, F R Deleo

  • 1Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA.

Insights

Human neutrophils initiate innate immunity but their inflammatory response termination is unclear. Genomics revealed an apoptosis differentiation program regulating neutrophil maturation and resolving bacterial infections.

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.

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