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Updated: Aug 12, 2026

Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro
Published on: January 25, 2017
An apoptosis differentiation programme in human polymorphonuclear leucocytes
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.
Abstract:
Human PMNs (polymorphonuclear leucocytes or neutrophils) are essential to the innate immune response against bacterial pathogens and are a key part of the acute inflammatory response. Although progress has been made, the molecular basis for termination of inflammation during bacterial infection in humans is largely undefined. To that end, we used genomics strategies to gain new insight into processes that facilitate resolution of neutrophil-mediated inflammation and bacterial infection. On the basis of a series of recent studies, we propose that global changes in PMN gene expression after phagocytosis comprise an apoptosis differentiation programme, which represents the final stage of transcription-regulated PMN maturation. Our studies indicate that the apoptosis differentiation programme regulates multiple post-phagocytic processes in human neutrophils, such as cell fate and proinflammatory activity, and is modulated by PMN-derived reactive oxygen species. Collectively, these studies establish a global model of host cell-pathogen interaction, which provides fundamental insight into the resolution of infection in humans.
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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