Elimination of Pseudomonas aeruginosa through Efferocytosis upon Binding to Apoptotic Cells

Darío Capasso1, María Victoria Pepe1, Jéssica Rossello2

  • 1Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde (IIB-INTECH), Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín, Buenos Aires, Argentina.

Plos Pathogens
|December 16, 2016
PubMed

Insights

Pseudomonas aeruginosa adheres to dead epithelial cells at junctions and is engulfed via efferocytosis. This process eliminates the bacteria, suggesting a host defense mechanism relevant to cystic fibrosis.

Area of Science:

  • Microbiology and Immunology
  • Cell Biology
  • Pathogen-Host Interactions

Background:

  • Mucosal barriers are critical defenses against opportunistic pathogens like Pseudomonas aeruginosa.
  • P. aeruginosa infections typically occur in individuals with compromised epithelial barriers.

Purpose of the Study:

  • To investigate the interaction of P. aeruginosa with polarized epithelial cells.
  • To elucidate the mechanisms of P. aeruginosa entry and intracellular fate within epithelial cells.
  • To explore the role of efferocytosis in controlling P. aeruginosa infection.

Main Methods:

  • Microscopy-based analysis of P. aeruginosa interaction with polarized epithelial cell monolayers.
  • Investigation of bacterial adherence to apoptotic and necrotic cells.
  • Characterization of bacterial internalization via efferocytosis and intracellular trafficking.

Main Results:

  • P. aeruginosa preferentially adheres to extruded apoptotic cells at multicellular junctions.
  • Bacterial tropism for dead cells is independent of the cell death type (apoptotic or necrotic).
  • P. aeruginosa is internalized through efferocytosis and resides within phagosomes that acquire lysosomal features, leading to bacterial killing.

Conclusions:

  • Efferocytosis serves as a host defense mechanism to eliminate P. aeruginosa.
  • This pathway is crucial for clearing bacteria associated with dead or dying epithelial cells.
  • Findings may inform strategies for treating infections in conditions like cystic fibrosis, marked by excessive cell death and impaired efferocytosis.

Related Concept Videos

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...
5.4K
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...
9.1K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
16.5K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
10.7K
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...
9.0K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.8K