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Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium.
Stephen B Kovacs1, Changhoon Oh2, Vivien I Maltez3
1Department of Immunology, Duke University, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA; Department of Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cell Reports
|July 30, 2020
Summary
Caspase-11 is essential for pyroptosis in neutrophils during Burkholderia thailandensis infection, unlike caspase-1. This highlights how cell type dictates inflammasome sensor outcomes and cell fate.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Pyroptosis, a form of programmed cell death, is triggered by inflammasome activation and gasdermin D cleavage.
- NLRC4 inflammasome activation in macrophages detects Burkholderia thailandensis, leading to IL-18 release and IFN-γ priming of caspase-11.
- IFN-γ is produced by natural killer (NK) and T cells.
Purpose of the Study:
- To investigate the distinct roles of caspase-1 and caspase-11 in pyroptosis across different immune cell types.
- To elucidate the cell-specific outcomes of inflammasome sensing during bacterial infection.
Main Methods:
- Macrophage and neutrophil inflammasome activation assays.
- Analysis of pyroptosis induction by caspase-1 and caspase-11.
- In vivo infection models using Burkholderia thailandensis in mice.
Main Results:
- Caspase-1 triggers pyroptosis in macrophages but not neutrophils upon NLRC4 activation.
- Caspase-11 induces pyroptosis in both macrophages and neutrophils.
- Caspase-11 is indispensable for neutrophil pyroptosis during B. thailandensis infection.
Conclusions:
- Inflammasome sensor pathways can elicit divergent cellular responses based on cell type.
- Cellular wiring determines the outcome of pathogen detection, influencing cell fate.
- Caspase-11 plays a critical, cell-specific role in host defense against bacterial pathogens.
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