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Updated: Jul 13, 2026
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities
Zane Orinska1, Marcus Maurer, Farhad Mirghomizadeh
1Department of Immunology and Cell Biology, Research Center Borstel, Parkallee 22, 23845 Borstel, Germany.
Abstract:
Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs express both constitutive and lipopolysaccharide-inducible IL-15 and store it intracellularly. Deletion of Il15 in mice markedly increases chymase activities, leading to greater MC bactericidal responses, increased processing and activation of neutrophil-recruiting chemokines, and significantly higher survival rates of mice after septic peritonitis. By showing that intracellular IL-15 acts as a specific negative transcriptional regulator of a mouse MC chymase (mast cell protease-2), we provide evidence that defined MC protease activity is transcriptionally regulated by an intracellularly retained cytokine. Our results identify an unexpected breach in MC-dependent innate immune defenses against sepsis and suggest that inhibiting intracellular IL-15 in MCs may improve survival from sepsis.
Insights
Interleukin-15 (IL-15) negatively regulates mast cell (MC) protease activity, crucial for innate immunity against sepsis. Inhibiting IL-15 in MCs may enhance survival from sepsis.
Area of Science:
- Immunology
- Microbiology
Background:
- Sepsis is a critical global health issue.
- Mast cells (MCs) play a role in innate immune defense against bacterial infections.
Purpose of the Study:
- To investigate the role of interleukin-15 (IL-15) in regulating mast cell protease activity during sepsis.
- To determine if IL-15 affects mast cell-dependent immune responses and survival in a sepsis model.
Main Methods:
- Utilized the mouse cecal ligation and puncture model to induce polymicrobial sepsis.
- Analyzed mast cell protease activity and chemokine processing in wild-type and Il15-deficient mice.
- Assessed survival rates following septic peritonitis.
Main Results:
- Mice lacking IL-15 exhibited increased mast cell chymase activity, enhanced bactericidal responses, and improved neutrophil chemokine activation.
- Intracellular IL-15 was identified as a negative transcriptional regulator of mast cell protease-2.
- Il15 deletion significantly increased survival rates in mice with septic peritonitis.
Conclusions:
- Mast cell protease activity is transcriptionally regulated by intracellular IL-15.
- Targeting intracellular IL-15 in mast cells presents a potential therapeutic strategy to improve sepsis survival.
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