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Updated: Jun 30, 2026
08:15
Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
Published on: April 11, 2025
Cytokines driven by caspase-1 and RIPK3 are antagonistic
Biorxiv : the Preprint Server for Biology
|June 29, 2026
Summary
Regulated cell death pathways offer redundant protection against pathogens. However, antagonistic cytokines, not cell death itself, determine infection outcomes by modulating immune responses.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Pyroptosis, apoptosis, and necroptosis are key cell death pathways.
- These pathways are believed to provide redundant protection against intracellular pathogens.
Purpose of the Study:
- To investigate the role of cell death pathways in host defense against cytosol-invasive bacteria.
- To determine the mechanisms underlying susceptibility and resistance during infection.
Main Methods:
- Mice lacking inflammasome signaling, caspase-8, and MLKL were used.
- Genetic deletion of Ripk3 was performed to assess its impact on resistance.
- Cytokine production (IL-1β and type I interferons) was analyzed.
Main Results:
- Mice lacking inflammasome signaling, caspase-8, and MLKL were susceptible to infection.
- Deletion of Ripk3 restored resistance, independent of cell death pathways.
- Susceptibility was linked to RIPK3-induced type I interferons, while IL-1β conferred resistance.
Conclusions:
- Host resistance to intracellular infection is dictated by antagonistic cytokines, not cell death.
- RIPK3-driven type I interferons can cause susceptibility unless counteracted by caspase-1-driven IL-1β.
- Cell death pathways contain cytokine-mediated immune regulatory functions distinct from cell death itself.
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01:17The Extrinsic Apoptotic Pathway
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01:16Necrosis
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