Related Experiment Video

Updated: Sep 20, 2026

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay
05:52

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay

Published on: May 12, 2023

Bacterial pathogens modulate an apoptosis differentiation program in human neutrophils

Scott D Kobayashi1, Kevin R Braughton, Adeline R Whitney

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

Proceedings of the National Academy of Sciences of the United States of America
|September 10, 2003
PubMed

Insights

Human neutrophils (PMNs) undergo apoptosis to resolve bacterial infections. However, Streptococcus pyogenes accelerates PMN apoptosis and necrosis, potentially aiding pathogen survival and disease progression.

Area of Science:

  • Immunology
  • Molecular Biology
  • Microbiology

Background:

  • Human polymorphonuclear leukocytes (PMNs), or neutrophils, are crucial for innate immunity against bacteria.
  • Neutrophil apoptosis aids in resolving inflammation during bacterial infections.
  • Transcriptional regulation of neutrophil apoptosis during infection remains poorly understood.

Purpose of the Study:

  • To investigate global gene expression changes in human PMNs during phagocytosis of various bacterial pathogens.
  • To identify molecular mechanisms underlying neutrophil apoptosis and its role in resolving bacterial infections.
  • To understand how different bacterial species influence neutrophil apoptosis and immune response.

Main Methods:

  • Global gene expression profiling of human PMNs after phagocytosis of Burkholderia cepacia, Borrelia hermsii, Listeria monocytogenes, Staphylococcus aureus, and Streptococcus pyogenes.
  • Analysis of gene expression patterns related to apoptosis and innate immune function.
  • Comparative analysis of neutrophil apoptosis kinetics and outcomes induced by different pathogens.

Main Results:

  • Phagocytosis of pathogenic bacteria induced a common neutrophil apoptosis differentiation program.
  • Genes for apoptosis effectors were upregulated, while immune receptors were downregulated.
  • Streptococcus pyogenes uniquely altered neutrophil gene expression, downregulating IFN-response genes and accelerating apoptosis followed by necrosis.

Conclusions:

  • Phagocytosis of bacteria typically induces a PMN apoptosis program that resolves infection.
  • Certain pathogens, like Streptococcus pyogenes, can subvert this program, leading to accelerated apoptosis, necrosis, and potential pathogen survival.
  • These distinct outcomes highlight two fundamental interactions between bacteria and neutrophils: resolution via apoptosis or immune evasion leading to disease.

More Related Videos

Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro10:05

Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro

Published on: January 25, 2017

A Simple and Efficient Method to Detect Nuclear Factor Activation in Human Neutrophils by Flow Cytometry08:26

A Simple and Efficient Method to Detect Nuclear Factor Activation in Human Neutrophils by Flow Cytometry

Published on: April 9, 2013

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...