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Updated: Aug 16, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei
Guang Wen Sun1, Jinhua Lu, Shazib Pervaiz
1Department of Biochemistry, National University of Singapore.
Abstract:
Burkholderia pseudomallei is the causative agent for melioidosis, an infectious disease endemic in South-east Asia and northern Australia. Infection can result in a wide spectrum of clinical outcomes, including asymtomatic, acute or chronic conditions. The ability of the bacteria to survive intracellularly within phagocytes and non-phagocytes is postulated to help this pathogen persist in the body during latent chronic conditions. In some Gram-negative bacteria, such as Shigella and Salmonella, the ability to evade macrophage killing involves inducing rapid macrophage cell death. In several of these instances, these bacteria activate cellular caspase-1 to induce cell death, which is increasingly described to exhibit features more characteristic of oncosis than classical apoptosis. We found that B. pseudomallei is also capable of inducing caspase-1 dependent death in macrophages and this process requires a functional bsa Type III Secretion System (TTSS). Bacterial internalization and pore formation in the cell membrane is necessary for death. Furthermore, cell death is accompanied by the release of IL-1beta and IL-18. We believe that this novel description of macrophage death induced by B. pseudomallei could shed light on the pathogenesis of the bacteria in disease.
Insights
Burkholderia pseudomallei causes melioidosis by inducing caspase-1 dependent macrophage death. This process, requiring the bsa Type III Secretion System (TTSS), involves bacterial internalization and IL-1beta/IL-18 release, impacting disease pathogenesis.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is prevalent in Southeast Asia and Australia.
- B. pseudomallei's intracellular survival aids chronic infection persistence.
- Some Gram-negative bacteria induce rapid macrophage death via caspase-1 to evade immune responses.
Purpose of the Study:
- To investigate if B. pseudomallei induces macrophage cell death.
- To elucidate the mechanisms and bacterial factors involved in this cell death process.
Main Methods:
- Macrophage cell culture and B. pseudomallei infection.
- Assessment of cell viability and death markers.
- Analysis of caspase-1 activation and cytokine release (IL-1beta, IL-18).
- Investigation of the role of the bsa Type III Secretion System (TTSS).
Main Results:
- B. pseudomallei induces caspase-1 dependent macrophage death.
- This cell death requires bacterial internalization and membrane pore formation.
- The bsa Type III Secretion System (TTSS) is essential for inducing this cell death.
- Macrophage death is associated with the release of IL-1beta and IL-18.
Conclusions:
- B. pseudomallei actively induces macrophage death through a TTSS-dependent mechanism.
- This novel form of cell death contributes to the pathogenesis of melioidosis.
- Understanding this interaction may reveal new therapeutic targets.
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