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Updated: May 8, 2026
06:52
Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Comparative insights into the apoptosome, inflammasomes and PIDDosome
Mohamed Lamkanfi1, Lieselotte Vande Walle2, Felix Eichin3
1Laboratory of Medical Immunology, Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium. Mohamed.Lamkanfi@UGent.be.
Nature Reviews. Immunology
|May 6, 2026
Summary
Caspase activation platforms like the apoptosome, inflammasome, and PIDDosome coordinate cellular stress responses. This review integrates their structures and functions, highlighting differences in triggers, localization, and roles in immunity and disease.
Area of Science:
- Cellular Biology
- Molecular Biology
- Immunology
Background:
- Caspase activation platforms (apoptosome, inflammasome, PIDDosome) are crucial for cellular stress responses, inflammation, and cell death.
- Existing research extensively studies these complexes individually, lacking a comparative perspective on their integrated functions.
Purpose of the Study:
- To provide an integrated review of the architecture, activation mechanisms, and signaling outputs of the apoptosome, inflammasome, and PIDDosome.
- To comparatively analyze the structural and functional principles of these supramolecular signaling platforms.
Main Methods:
- Integrated literature review and comparative analysis of existing research on caspase activation platforms.
- Examination of domain architecture, activation mechanisms, subcellular localization, upstream triggers, and downstream effectors.
Main Results:
- All three platforms share conserved domain architecture and induce proximity-dependent caspase activation.
- Key differences lie in their subcellular localization, upstream triggers, and downstream signaling roles in immunity, cell cycle, and homeostasis.
Conclusions:
- Understanding these platforms comparatively reveals shared and distinct principles governing cellular stress responses.
- Dysregulation due to mutations links these complexes to cancer, immune disorders, and neurodevelopmental conditions, suggesting therapeutic potential.
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01:17Phagocytosis 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.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
01:31The 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...
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:17The 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...
01:30Apoptosis
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 reduction of the tissue.