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Clinical isolates of Shigella species induce apoptosis in macrophages
1Skirball Institute, Department of Microbiology, and Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA.
Abstract:
Shigella species are invasive enterobacteria that cause dysentery, a severe form of diarrhea. The ability to invade epithelial cells and to kill macrophages is essential for virulence in a prototype Shigella flexneri strain. It is shown here that clinical isolates of both S. flexneri and Shigella sonnei invade epithelial cells and are cytotoxic to macrophages in vitro. Furthermore, clinical Shigella strains kill macrophages by inducing apoptosis. The conservation of the ability to induce macrophage apoptosis by clinical isolates suggests that this function plays a crucial role in the pathogenesis of Shigella species.
Insights
Shigella bacteria cause severe diarrhea by invading cells and killing immune cells. Clinical Shigella isolates induce apoptosis in macrophages, highlighting a key role in disease pathogenesis.
Area of Science:
- Microbiology
- Pathogenesis
- Immunology
Background:
- Shigella species are invasive enterobacteria responsible for dysentery, a severe diarrheal disease.
- Virulence in Shigella flexneri relies on epithelial cell invasion and macrophage killing.
- Understanding Shigella pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the virulence mechanisms of clinical Shigella isolates.
- To determine if clinical Shigella strains exhibit epithelial cell invasion and macrophage cytotoxicity.
- To elucidate the role of macrophage apoptosis in Shigella pathogenesis.
Main Methods:
- In vitro assays to assess epithelial cell invasion by clinical Shigella isolates.
- Macrophage cytotoxicity assays using clinical Shigella strains.
- Apoptosis assays to detect programmed cell death in macrophages.
Main Results:
- Clinical isolates of Shigella flexneri and Shigella sonnei demonstrated epithelial cell invasion.
- These clinical strains were cytotoxic to macrophages in vitro.
- Shigella-induced macrophage death occurred via apoptosis.
Conclusions:
- The ability to invade epithelial cells and induce macrophage apoptosis is conserved among clinical Shigella isolates.
- Macrophage apoptosis is a critical virulence factor in Shigella pathogenesis.
- These findings provide insights into the molecular mechanisms underlying Shigella infections.