The Orchestra and Its Maestro: Shigella's Fine-Tuning of the Inflammasome Platforms
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Anna-Karin Hermansson1, Ida Paciello1, Maria Lina Bernardini2,3
1Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza-Università di Roma, Piazzale Aldo Moro, 5, 00185, Rome, Italy.
Abstract:
Shigella spp. are the causative agents of bacillary dysentery, leading to extensive mortality and morbidity worldwide. These facultative intracellular bacteria invade the epithelium of the colon and the rectum, inducing a severe inflammatory response from which the symptoms of the disease originate. Shigella are human pathogens able to manipulate and subvert the innate immune system surveillance. Shigella dampens inflammasome activation in epithelial cells. In infected macrophages, inflammasome activation and IL-1β and IL-18 release lead to massive neutrophil recruitment and greatly contribute to inflammation. Here, we describe how Shigella hijacks and finely tunes inflammasome activation in the different cell populations involved in pathogenesis: epithelial cells, macrophages, neutrophils, DCs, and B and T lymphocytes. Shigella emerges as a "sly" pathogen that switches on/off the inflammasome mechanisms in order to optimize the interaction with the host and establish a successful infection.
Insights
Shigella bacteria manipulate inflammasome activation in various host cells during infection. This "sly" pathogen controls inflammation to establish a successful Shigella infection.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis
Background:
- Shigella spp. cause bacillary dysentery, a significant global health concern.
- These bacteria invade host cells, triggering inflammatory responses and disease symptoms.
- Shigella actively subverts the host's innate immune system surveillance.
Purpose of the Study:
- To investigate how Shigella manipulates inflammasome activation across different host cell types.
- To understand the role of inflammasome tuning in Shigella pathogenesis.
- To elucidate Shigella's strategy for optimizing host interaction and infection establishment.
Main Methods:
- Analysis of inflammasome activation in epithelial cells and immune cells (macrophages, neutrophils, DCs, lymphocytes) upon Shigella infection.
- Investigation of cytokine release (IL-1β, IL-18) and its impact on inflammation.
- Characterization of Shigella's molecular mechanisms for controlling inflammasome pathways.
Main Results:
- Shigella dampens inflammasome activation in epithelial cells.
- In macrophages, Shigella promotes inflammasome activation, leading to IL-1β/IL-18 release and neutrophil recruitment.
- The study details Shigella's dynamic control of inflammasome activity across diverse cell populations.
Conclusions:
- Shigella employs a sophisticated strategy to modulate host inflammasome responses.
- This pathogen "switches on/off" inflammasome mechanisms to facilitate its interaction with the host.
- Fine-tuning inflammasome activation is crucial for successful Shigella infection and disease progression.
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